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Yang F, Chi R, Zhang R, Liu K, Wang P, Di R, He X, Wang X, Liu Y, Chu M. A Novel ceRNA Axis LOC121818100/Novel-miR-400/SSRP1 Regulated Muscle Growth and Injury Repair in Sheep. J Cachexia Sarcopenia Muscle 2025; 16:e13836. [PMID: 40468947 PMCID: PMC12138275 DOI: 10.1002/jcsm.13836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 02/28/2025] [Accepted: 04/06/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND In mammals, skeletal muscle growth is a delicate process. The construction of competitive endogenous RNA (ceRNA) networks provides an effective way to analyse the molecular mechanism of complex trait formation. The aim of this study was to investigate the role of the ceRNA axis in skeletal muscle development. METHODS Transcriptome sequencing (RNA-seq) technology was used to analyse the RNA expression profile of longissimus dorsi muscle of different breeds of sheep. MiRanda and qTar databases were used to construct the ceRNA network. The key ceRNA regulatory axis was screened by bioinformatics analysis. Using primary sheep myoblast (SMs) and mouse models, we evaluated the effects of target gene structure specific recognition protein 1 (SSRP1) and related noncoding RNA (ncRNA) on cell proliferation and muscle development in vitro and in vivo functional experiments. Dual-luciferase reporter assay, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assay were used for mechanistic analysis. RESULTS The number of differentially expressed (DE) lncRNA, miRNA and mRNA in STH and SNT sheep (n = 5) longissimus dorsi muscle was 99, 53 and 1864, respectively (p < 0.05). A ceRNA network containing 146 lncRNA-miRNA-mRNA axes was constructed (p < 0.05). Bioinformatics analysis showed that LOC121818100/Novel-miR-400/SSRP1 was most correlated with skeletal muscle development (p < 0.05). Analysis in SMs showed that the expression of proliferation markers (CCND1, CCNE1, PCNA and PAX7) was decreased (-30%, p < 0.05) after inhibition of LOC121818100 or SSRP1 expression. Overexpression of Novel-miR-400 decreased the expression of proliferation markers (-80%, p < 0.01). SSRP1 knockdown decreased the proliferation activity of SMs (-80%, p < 0.05). After SSRP1 knockdown, the proportion of SMs entering S phase decreased (-3.22%, p < 0.05). 5-ethynyl-2'-deoxyuridine (EdU) analysis showed the same trend (p < 0.05). The results of mouse model also confirmed that SSRP1 was positively correlated with skeletal muscle development (p < 0.05). It was confirmed that LOC121818100 acts as a sponge for Novel-miR-400 and reduces its inhibitory effect on SSRP1. This interaction promotes skeletal muscle development in sheep. CONCLUSION Our results identified a role for SSRP1 in promoting skeletal muscle growth. Sheep skeletal muscle development is regulated by LOC121818100/Novel-miR-400/SSRP1 axis. These findings provide new insights into the role of the ceRNA machinery in regulating skeletal muscle growth.
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Affiliation(s)
- Fan Yang
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
- College of BioengineeringChongqing UniversityChongqingChina
| | - Runqing Chi
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Runan Zhang
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Kai Liu
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Pingqing Wang
- College of BioengineeringChongqing UniversityChongqingChina
| | - Ran Di
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Xiaoyun He
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Xiangyu Wang
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Yufang Liu
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
| | - Mingxing Chu
- State Key Laboratory of Animal Biotech BreedingInstitute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS)BeijingChina
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Vrbnjak K, Sewduth RN. Multi-Omic Approaches in Cancer-Related Micropeptide Identification. Proteomes 2024; 12:26. [PMID: 39311199 PMCID: PMC11417835 DOI: 10.3390/proteomes12030026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/02/2024] [Accepted: 09/11/2024] [Indexed: 09/26/2024] Open
Abstract
Despite the advances in modern cancer therapy, malignant diseases are still a leading cause of morbidity and mortality worldwide. Conventional treatment methods frequently lead to side effects and drug resistance in patients, highlighting the need for novel therapeutic approaches. Recent findings have identified the existence of non-canonical micropeptides, an additional layer of the proteome complexity, also called the microproteome. These small peptides are a promising class of therapeutic agents with the potential to address the limitations of current cancer treatments. The microproteome is encoded by regions of the genome historically annotated as non-coding, and its existence has been revealed thanks to recent advances in proteomic and bioinformatic technology, which dramatically improved the understanding of proteome complexity. Micropeptides have been shown to be biologically active in several cancer types, indicating their therapeutic role. Furthermore, they are characterized by low toxicity and high target specificity, demonstrating their potential for the development of better tolerated drugs. In this review, we survey the current landscape of known micropeptides with a role in cancer progression or treatment, discuss their potential as anticancer agents, and describe the methodological challenges facing the proteome field of research.
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Affiliation(s)
- Katarina Vrbnjak
- VIB-KU Leuven Center for Cancer Biology (VIB), 3000 Leuven, Belgium
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Kim Y, Ha H, Kim K. Discovery of high-expressing lncRNA-derived sORFs as potential tumor-associated antigens in hepatocellular carcinoma. Genes Genomics 2024; 46:1085-1095. [PMID: 39112833 DOI: 10.1007/s13258-024-01549-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 07/15/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND This study is based on deep mining of Ribo-seq data for the identification of lncRNAs that have highly expressed sORFs in HCC. In this paper, dynamic prospects associated with sORFs acting as newly defined tumor-specific epitopes are discussed with possible improvement in strategies for tumor immunotherapy. OBJECTIVE Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy. METHODS MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes. RESULTS Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981. CONCLUSIONS This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.
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Affiliation(s)
- Yooeun Kim
- Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
| | - Hongseok Ha
- Institute of Endemic Disease, Seoul National University Medical Research Center, Seoul, Republic of Korea
| | - Kwangsoo Kim
- Department of Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- Department of Transdisciplinary Medicine, Institute of Convergence Medicine with Innovative Technology, Seoul National University Hospital, Seoul, Republic of Korea.
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Ding S, Liao H, Huang F, Chen L, Guo W, Feng K, Huang T, Cai YD. Analyzing domain features of small proteins using a machine-learning method. Proteomics 2024; 24:e2300302. [PMID: 38258387 DOI: 10.1002/pmic.202300302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 01/14/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024]
Abstract
Small proteins (SPs) are a unique group of proteins that play crucial roles in many important biological processes. Exploring the biological function of SPs is necessary. In this study, the InterPro tool and the maximum correlation method were utilized to analyze functional domains of SPs. The purpose was to identify important functional domains that can indicate the essential differences between small and large protein sequences. First, the small and large proteins were represented by their functional domains via a one-hot scheme. Then, the MaxRel method was adopted to evaluate the relationships between each domain and the target variable, indicating small or large protein. The top 36 domain features were selected for further investigation. Among them, 14 were deemed to be highly related to SPs because they were annotated to SPs more frequently than large proteins. We found the involvement of functional domains, such as ubiquitin-conjugating enzyme/RWD-like, nuclear transport factor 2 domain, and alpha subunit of guanine nucleotide-binding protein (G-protein) in regulating the biological function of SPs. The involvement of these domains has been confirmed by other recent studies. Our findings indicate that protein functional domains may regulate small protein-related functions and predict their biological activity.
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Affiliation(s)
- ShiJian Ding
- School of Life Sciences, Shanghai University, Shanghai, China
| | | | - FeiMing Huang
- School of Life Sciences, Shanghai University, Shanghai, China
| | - Lei Chen
- College of Information Engineering, Shanghai Maritime University, Shanghai, China
| | - Wei Guo
- Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
| | - KaiYan Feng
- Department of Computer Science, Guangdong AIB Polytechnic College, Guangzhou, China
| | - Tao Huang
- Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Yu-Dong Cai
- School of Life Sciences, Shanghai University, Shanghai, China
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Zhang D, Ma Y, Naz M, Ahmed N, Zhang L, Zhou JJ, Yang D, Chen Z. Advances in CircRNAs in the Past Decade: Review of CircRNAs Biogenesis, Regulatory Mechanisms, and Functions in Plants. Genes (Basel) 2024; 15:958. [PMID: 39062737 PMCID: PMC11276256 DOI: 10.3390/genes15070958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/12/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control.
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Affiliation(s)
- Dongqin Zhang
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
| | - Yue Ma
- College of Agriculture, Guizhou University, Guiyang 550025, China;
| | - Misbah Naz
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
| | - Nazeer Ahmed
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
| | - Libo Zhang
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
| | - Jing-Jiang Zhou
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
- Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK
| | - Ding Yang
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
| | - Zhuo Chen
- Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China; (D.Z.); (M.N.); (N.A.); (L.Z.); (J.-J.Z.); (D.Y.)
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Wen K, Chen X, Gu J, Chen Z, Wang Z. Beyond traditional translation: ncRNA derived peptides as modulators of tumor behaviors. J Biomed Sci 2024; 31:63. [PMID: 38877495 PMCID: PMC11177406 DOI: 10.1186/s12929-024-01047-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 05/24/2024] [Indexed: 06/16/2024] Open
Abstract
Within the intricate tapestry of molecular research, noncoding RNAs (ncRNAs) were historically overshadowed by a pervasive presumption of their inability to encode proteins or peptides. However, groundbreaking revelations have challenged this notion, unveiling select ncRNAs that surprisingly encode peptides specifically those nearing a succinct 100 amino acids. At the forefront of this epiphany stand lncRNAs and circRNAs, distinctively characterized by their embedded small open reading frames (sORFs). Increasing evidence has revealed different functions and mechanisms of peptides/proteins encoded by ncRNAs in cancer, including promotion or inhibition of cancer cell proliferation, cellular metabolism (glucose metabolism and lipid metabolism), and promotion or concerted metastasis of cancer cells. The discoveries not only accentuate the depth of ncRNA functionality but also open novel avenues for oncological research and therapeutic innovations. The main difficulties in the study of these ncRNA-derived peptides hinge crucially on precise peptide detection and sORFs identification. Here, we illuminate cutting-edge methodologies, essential instrumentation, and dedicated databases tailored for unearthing sORFs and peptides. In addition, we also conclude the potential of clinical applications in cancer therapy.
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Affiliation(s)
- Kang Wen
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, P.R. China
| | - Xin Chen
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, P.R. China
| | - Jingyao Gu
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, P.R. China
| | - Zhenyao Chen
- Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, P.R. China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
| | - Zhaoxia Wang
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, P.R. China.
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Zhou H, Wu Y, Cai J, Zhang D, Lan D, Dai X, Liu S, Song T, Wang X, Kong Q, He Z, Tan J, Zhang J. Micropeptides: potential treatment strategies for cancer. Cancer Cell Int 2024; 24:134. [PMID: 38622617 PMCID: PMC11020647 DOI: 10.1186/s12935-024-03281-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/23/2024] [Indexed: 04/17/2024] Open
Abstract
Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.
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Affiliation(s)
- He Zhou
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Yan Wu
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Ji Cai
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Dan Zhang
- Zunyi Medical University Library, Zunyi, 563000, China
| | - Dongfeng Lan
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Xiaofang Dai
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Songpo Liu
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Tao Song
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Xianyao Wang
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China
| | - Qinghong Kong
- Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi563000, China
| | - Zhixu He
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, 563000, China.
| | - Jun Tan
- Department of Histology and Embryology, Zunyi Medical University, Zunyi, 563000, China.
| | - Jidong Zhang
- Department of Immunology, Zunyi Medical University, Zunyi City, Guizhou Province, 563000, China.
- Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China.
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, 563000, China.
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Mohapatra S, Banerjee A, Rausseo P, Dragomir MP, Manyam GC, Broom BM, Calin GA. FuncPEP v2.0: An Updated Database of Functional Short Peptides Translated from Non-Coding RNAs. Noncoding RNA 2024; 10:20. [PMID: 38668378 PMCID: PMC11054400 DOI: 10.3390/ncrna10020020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 04/29/2024] Open
Abstract
Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the categorization of host ncRNAs. FuncPEP v2.0 contains 152 functional ncPEPs, out of which 40 are novel entries. A PubMed search from August 2020 to July 2023 incorporating specific keywords was performed and screened for publications reporting validated functional peptides derived from ncRNAs. We did not observe a significant increase in newly discovered functional ncPEPs, but a steady increase. The novel identified ncPEPs included in the database were characterized by a wide array of molecular and physiological parameters (i.e., types of host ncRNA, species distribution, chromosomal density, distribution of ncRNA length, identification methods, molecular weight, and functional distribution across humans and other species). We consider that, despite the fact that MS can now easily identify ncPEPs, there still are important limitations in proving their functionality.
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Affiliation(s)
- Swati Mohapatra
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (S.M.); (P.R.)
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA;
| | - Anik Banerjee
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA;
- Department of Neurology, University of Texas McGovern Medical School, Houston, TX 77030, USA
| | - Paola Rausseo
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (S.M.); (P.R.)
- Scripps College, Claremont, CA 91711, USA
| | - Mihnea P. Dragomir
- Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany;
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Berlin Institute of Health at Charité, 10117 Berlin, Germany
| | - Ganiraju C. Manyam
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (G.C.M.)
| | - Bradley M. Broom
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (G.C.M.)
| | - George A. Calin
- Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (S.M.); (P.R.)
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Cabrera-Najera LE, Chirino-Galindo G, Palomar-Morales M. Participation of lncRNAs in the development of diabetic complications: Systematic review and meta-analysis. I. Rat. Diabet Med 2024; 41:e15244. [PMID: 37846767 DOI: 10.1111/dme.15244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/08/2023] [Accepted: 10/12/2023] [Indexed: 10/18/2023]
Abstract
AIMS We evaluated the involvement of lncRNAs in the development of pathologies associated with chronic hyperglycaemia in rat models in a model of type 1, type 2 and gestational diabetes. METHODS Reports were searched in Dialnet, Scielo, HINARI, Springer, ClinicalKey, OTseeker, PubMed and different grey literature databases with any restrictions. Bibliography databases will be searched from their inception to December 2022. RESULTS Thirty-seven studies met our criteria, and they had the following characteristics: original experimental studies on diabetes, the lncRNAs were extracted or measured from tissues of specific areas and the results were expressed in terms of standard measures by RT-PCR. In most studies, both primary and secondary outcomes were mentioned. On the other hand, we found a total of nine diabetic complications, being retinopathy, nephropathy and neuropathy the most representatives. Additionally, it was found that MALAT1, H19, NEAT1 and TUG1 are the most studied lncRNAs about these complications in rats. On the other hand, the lncRNAs with the highest rate of change were MSTRG.1662 (17.85; 13.78, 21.93), ENSRNOT00000093120_Aox3 (7.13; 5.95, 8.31) and NONRATG013497.2 (-5.55; -7.18, -3.93). CONCLUSIONS This review found a significant involvement of lncRNAs in the progression of pathologies associated with chronic hyperglycaemia in rat models, and further studies are needed to establish their potential as biomarkers and therapeutic targets for diabetes.
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Affiliation(s)
- Leonardo-Elias Cabrera-Najera
- Laboratorio de Metabolismo de la Diabetes Mellitus, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
| | - Gladys Chirino-Galindo
- Laboratorio de Metabolismo de la Diabetes Mellitus, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
| | - Martín Palomar-Morales
- Laboratorio de Metabolismo de la Diabetes Mellitus, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
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Seyhan AA. Trials and Tribulations of MicroRNA Therapeutics. Int J Mol Sci 2024; 25:1469. [PMID: 38338746 PMCID: PMC10855871 DOI: 10.3390/ijms25031469] [Citation(s) in RCA: 105] [Impact Index Per Article: 105.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/12/2024] Open
Abstract
The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Consequently, RNA therapeutics have emerged as highly adaptable and modular options for cancer therapy. Moreover, advancements in RNA chemistry and delivery methods have been pivotal in shaping the landscape of RNA-based immunotherapy, including miRNA-based approaches. Consequently, the biotechnology and pharmaceutical industry has witnessed a resurgence of interest in incorporating RNA-based immunotherapies and miRNA therapeutics into their development programs. Despite substantial progress in preclinical research, the field of miRNA-based therapeutics remains in its early stages, with only a few progressing to clinical development, none reaching phase III clinical trials or being approved by the US Food and Drug Administration (FDA), and several facing termination due to toxicity issues. These setbacks highlight existing challenges that must be addressed for the broad clinical application of miRNA-based therapeutics. Key challenges include establishing miRNA sensitivity, specificity, and selectivity towards their intended targets, mitigating immunogenic reactions and off-target effects, developing enhanced methods for targeted delivery, and determining optimal dosing for therapeutic efficacy while minimizing side effects. Additionally, the limited understanding of the precise functions of miRNAs limits their clinical utilization. Moreover, for miRNAs to be viable for cancer treatment, they must be technically and economically feasible for the widespread adoption of RNA therapies. As a result, a thorough risk evaluation of miRNA therapeutics is crucial to minimize off-target effects, prevent overdosing, and address various other issues. Nevertheless, the therapeutic potential of miRNAs for various diseases is evident, and future investigations are essential to determine their applicability in clinical settings.
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Affiliation(s)
- Attila A. Seyhan
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA;
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI 02912, USA
- Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
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11
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Tan W, Ma J, Fu J, Wu B, Zhu Z, Huang X, Du M, Wu C, Balawi E, Zhou Q, Zhang J, Liao Z. Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice. Neural Regen Res 2024; 19:171-179. [PMID: 37488864 PMCID: PMC10479836 DOI: 10.4103/1673-5374.374135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 02/04/2023] [Accepted: 03/11/2023] [Indexed: 07/26/2023] Open
Abstract
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury. However, the precise mechanism of action remains unclear. In this study, we induced moderate traumatic brain injury in mice by intraperitoneal injection of erythropoietin for 3 consecutive days. RNA sequencing detected a total of 4065 differentially expressed RNAs, including 1059 mRNAs, 92 microRNAs, 799 long non-coding RNAs, and 2115 circular RNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway, Wnt pathway, and MAPK pathway. Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs. Because the axon guidance pathway was repeatedly enriched, the expression of Wnt5a and Ephb6, key factors in the axonal guidance pathway, was assessed. Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury, and these effects were reversed by treatment with erythropoietin. These findings suggest that erythropoietin can promote recovery of nerve function after traumatic brain injury through the axon guidance pathway.
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Affiliation(s)
- Weilin Tan
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jun Ma
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jiayuanyuan Fu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Biying Wu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ziyu Zhu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xuekang Huang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mengran Du
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chenrui Wu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ehab Balawi
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qiang Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jie Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhengbu Liao
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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12
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Ruan X, Liu Y, Wang P, Liu L, Ma T, Xue Y, Dong W, Zhao Y, E T, Lin H, Wang D, Yang C, Song J, Liu J, Deng M, An P, Lin Y, Yang J, Cui Z, Cao Y, Liu X. RBMS3-induced circHECTD1 encoded a novel protein to suppress the vasculogenic mimicry formation in glioblastoma multiforme. Cell Death Dis 2023; 14:745. [PMID: 37968257 PMCID: PMC10651854 DOI: 10.1038/s41419-023-06269-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 10/09/2023] [Accepted: 11/03/2023] [Indexed: 11/17/2023]
Abstract
Glioblastoma multiforme (GBM) is a highly vascularized malignant cancer of the central nervous system, and the presence of vasculogenic mimicry (VM) severely limits the effectiveness of anti-vascular therapy. In this study, we identified downregulated circHECTD1, which acted as a key VM-suppressed factor in GBM. circHECTD1 elevation significantly inhibited cell proliferation, migration, invasion and tube-like structure formation in GBM. RIP assay was used to demonstrate that the flanking intron sequence of circHECTD1 can be specifically bound by RBMS3, thereby inducing circHECTD1 formation to regulate VM formation in GBM. circHECTD1 was confirmed to possess a strong protein-encoding capacity and the encoded functional peptide 463aa was identified by LC-MS/MS. Both circHECTD1 and 463aa significantly inhibited GBM VM formation in vivo and in vitro. Analysis of the 463aa protein sequence revealed that it contained a ubiquitination-related domain and promoted NR2F1 degradation by regulating the ubiquitination of the NR2F1 at K396. ChIP assay verified that NR2F1 could directly bind to the promoter region of MMP2, MMP9 and VE-cadherin, transcriptionally promoting the expression of VM-related proteins, which in turn enhanced VM formation in GBM. In summary, we clarified a novel pathway for RBMS3-induced circHECTD1 encoding functional peptide 463aa to mediate the ubiquitination of NR2F1, which inhibited VM formation in GBM. This study aimed to reveal new mechanisms of GBM progression in order to provide novel approaches and strategies for the anti-vascular therapy of GBM. The schematic illustration showed the inhibitory effect of circHECTD1-463aa in the VM formation in GBM.
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Affiliation(s)
- Xuelei Ruan
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Yunhui Liu
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Ping Wang
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Libo Liu
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Teng Ma
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Yixue Xue
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Weiwei Dong
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Yubo Zhao
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Tiange E
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Hongda Lin
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Di Wang
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Chunqing Yang
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Jian Song
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Jiate Liu
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Meiqi Deng
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Ping An
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Yang Lin
- Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
| | - Jin Yang
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Zheng Cui
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Yaming Cao
- Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.
| | - Xiaobai Liu
- Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China.
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
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13
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Zhang M, Zhao J, Wu J, Wang Y, Zhuang M, Zou L, Mao R, Jiang B, Liu J, Song X. In-depth characterization and identification of translatable lncRNAs. Comput Biol Med 2023; 164:107243. [PMID: 37453378 DOI: 10.1016/j.compbiomed.2023.107243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/16/2023] [Accepted: 07/07/2023] [Indexed: 07/18/2023]
Abstract
Long non-coding RNAs (LncRNAs) are non-protein coding transcripts more than 200 nucleotides in length. Deep sequencing technologies have unveiled lncRNAs can harbor translatable short open reading frames (sORFs). Yet the regulatory mechanisms governing lncRNA translation events remain poorly understood. Here, we exhaustively detected the sequence, functional element, and structure features relevant to lncRNA translation in human. Extensive identification and analysis reveal that translatable lncRNAs contain richer protein-coding related sequence features, cap-dependent and cap-independent translation initiation mechanisms, and more stable secondary structures, as compared to untranslatable lncRNAs. These findings strongly support lncRNAs serve as a repository for the production of new small peptides. Based on the feature fusion affecting translation and the extreme gradient boosting (XGBoost) algorithm, we developed the first computational tool that dedicated for predicting translatable lncRNAs, named TransLncPred. Benchmark experimental results show that our method outperforms several state-of-the-art RNA coding potential prediction tools on the same training and testing datasets. The 100-time 10-fold cross-validation tests also demonstrate that regulatory element-derived features, especially N7-methylguanosine (m7G) and internal ribosome entry site (IRES), contribute to the improvement in predictive performance.
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Affiliation(s)
- Meng Zhang
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Jian Zhao
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
| | - Jing Wu
- School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, China
| | - Yulan Wang
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Minhui Zhuang
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Lingxiao Zou
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Renlong Mao
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Bin Jiang
- College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Jingjing Liu
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China
| | - Xiaofeng Song
- Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
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14
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Seyhan AA. Circulating microRNAs as Potential Biomarkers in Pancreatic Cancer-Advances and Challenges. Int J Mol Sci 2023; 24:13340. [PMID: 37686149 PMCID: PMC10488102 DOI: 10.3390/ijms241713340] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/21/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
There is an urgent unmet need for robust and reliable biomarkers for early diagnosis, prognosis, and prediction of response to specific treatments of many aggressive and deadly cancers, such as pancreatic cancer, and liquid biopsy-based miRNA profiling has the potential for this. MiRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many cancers, functioning as either oncomes or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling of dysregulated miRNAs in pancreatic cancer has been shown to correlate with disease diagnosis, indicate optimal treatment options and predict response to a specific therapy. Specific miRNA signatures can track the stages of pancreatic cancer and hold potential as diagnostic, prognostic, and predictive markers, as well as therapeutics such as miRNA mimics and miRNA inhibitors (antagomirs). Furthermore, identified specific miRNAs and genes they regulate in pancreatic cancer along with downstream pathways can be used as potential therapeutic targets. However, a limited understanding and validation of the specific roles of miRNAs, lack of tissue specificity, methodological, technical, or analytical reproducibility, harmonization of miRNA isolation and quantification methods, the use of standard operating procedures, and the availability of automated and standardized assays to improve reproducibility between independent studies limit bench-to-bedside translation of the miRNA biomarkers for clinical applications. Here I review recent findings on miRNAs in pancreatic cancer pathogenesis and their potential as diagnostic, prognostic, and predictive markers.
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Affiliation(s)
- Attila A. Seyhan
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA;
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI 02912, USA
- Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
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15
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Wang X, Zhang Z, Shi C, Wang Y, Zhou T, Lin A. Clinical prospects and research strategies of long non-coding RNA encoding micropeptides. Zhejiang Da Xue Xue Bao Yi Xue Ban 2023; 52:397-405. [PMID: 37643974 PMCID: PMC10495248 DOI: 10.3724/zdxbyxb-2023-0128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 07/20/2023] [Indexed: 08/12/2023]
Abstract
Long non-coding RNAs (lncRNAs) which are usually thought to have no protein coding ability, are widely involved in cell proliferation, signal transduction and other biological activities. However, recent studies have suggested that short open reading frames (sORFs) of some lncRNAs can encode small functional peptides (micropeptides). These micropeptides appear to play important roles in calcium homeostasis, embryonic development and tumorigenesis, suggesting their potential as therapeutic targets and diagnostic biomarkers. Currently, bioinformatic tools as well as experimental methods such as ribosome mapping and in vitro translation are applied to predict the coding potential of lncRNAs. Furthermore, mass spectrometry, specific antibodies and epitope tags are used for validating the expression of micropeptides. Here, we review the physiological and pathological functions of recently identified micropeptides as well as research strategies for predicting the coding potential of lncRNAs to facilitate the further research of lncRNA encoded micropeptides.
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Affiliation(s)
- Xinyi Wang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University Cancer Center, Hangzhou 310058, China.
| | - Zhen Zhang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Zhejiang University Cancer Center, Hangzhou 310058, China
| | - Chengyu Shi
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Zhejiang University Cancer Center, Hangzhou 310058, China
| | - Ying Wang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Zhejiang University Cancer Center, Hangzhou 310058, China
| | - Tianhua Zhou
- Zhejiang University Cancer Center, Hangzhou 310058, China.
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Center for RNA Medicine, International Institutes of Medicine, Zhejiang University, Jinhua 322000, Zhejiang Province, China.
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
| | - Aifu Lin
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University Cancer Center, Hangzhou 310058, China.
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Center for RNA Medicine, International Institutes of Medicine, Zhejiang University, Jinhua 322000, Zhejiang Province, China.
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16
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Ye M, Gao R, Chen S, Bai J, Chen J, Lu F, Gu D, Shi X, Yu P, Tian Y, Tang Q, Dong K. FAM201A encodes small protein NBASP to inhibit neuroblastoma progression via inactivating MAPK pathway mediated by FABP5. Commun Biol 2023; 6:714. [PMID: 37438449 DOI: 10.1038/s42003-023-05092-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 07/03/2023] [Indexed: 07/14/2023] Open
Abstract
Increasing evidence indicates that long non-coding RNA (lncRNA) is one of the most important RNA regulators in the pathogenesis of neuroblastoma (NB). Here, we found that FAM201A was low expressed in NB and a variety of gain and loss of function studies elucidated the anti-tumor effects of FAM201A on the regulation of proliferation, migration and invasion of NB cells. Intriguingly, we identified the ability of FAM201A to encode the tumor-suppressing protein, NBASP, which interacted with FABP5 and negatively regulated its expression. In vivo assays also revealed NBASP repressed NB growth via inactivating MAPK pathway mediated by FABP5. In conclusion, our findings demonstrated that NBASP encoded by FAM201A played a tumor-suppressor role in NB carcinogenesis via down-regulating FABP5 to inactivate the MAPK pathway. These results extended our understanding of the relationship of lncRNA-encoded functional peptides and plasticity of tumor progression.
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Affiliation(s)
- Mujie Ye
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
- Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Runnan Gao
- Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Shiyu Chen
- Department of Biochemistry and Molecular Biology, Research Center for Birth Defects, Institutes of Biomedical Sciences, Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jianan Bai
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Jinhao Chen
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Feiyu Lu
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Danyang Gu
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Xiaoting Shi
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Ping Yu
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Ye Tian
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China
| | - Qiyun Tang
- Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China.
| | - Kuiran Dong
- Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
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17
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Loan Young T, Chang Wang K, James Varley A, Li B. Clinical Delivery of Circular RNA: Lessons Learned from RNA Drug Development. Adv Drug Deliv Rev 2023; 197:114826. [PMID: 37088404 DOI: 10.1016/j.addr.2023.114826] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/28/2023] [Accepted: 04/11/2023] [Indexed: 04/25/2023]
Abstract
Circular RNAs (circRNA) represent a distinct class of covalently closed-loop RNA molecules, which play diverse roles in regulating biological processes and disease states. The enhanced stability of synthetic circRNAs compared to their linear counterparts has recently garnered considerable research interest, paving the way for new therapeutic applications. While clinical circRNA technology is still in its early stages, significant advancements in mRNA technology offer valuable insights into its potential future applications. Two primary obstacles that must be addressed are the development of efficient production methods and the optimization of delivery systems. To expedite progress in this area, this review aims to provide an overview of the current state of knowledge on circRNA structure and function, outline recent techniques for synthesizing circRNAs, highlight key delivery strategies and applications, and discuss the current challenges and future prospects in the field of circRNA-based therapeutics.
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Affiliation(s)
- Tiana Loan Young
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
| | - Kevin Chang Wang
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
| | - Andrew James Varley
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
| | - Bowen Li
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3M2, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2C1, Canada.
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18
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Ren ZL, Kang XD, Zheng YX, Shi HF, Chen CA, Shi YY, Wang QG, Cheng FF, Wang XQ, Li CX. Emerging effects of non-coding RNA in vascular endothelial cells during strokes. Vascul Pharmacol 2023; 150:107169. [PMID: 37059212 DOI: 10.1016/j.vph.2023.107169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 02/05/2023] [Accepted: 03/24/2023] [Indexed: 04/16/2023]
Abstract
Vascular and neurological damage are the typical outcomes of ischemic strokes. Vascular endothelial cells (VECs), a substantial component of the blood-brain barrier (BBB), are necessary for normal cerebrovascular physiology. During an ischemic stroke (IS), changes in the brain endothelium can lead to a BBB rupture, inflammation, and vasogenic brain edema, and VECs are essential for neurotrophic effects and angiogenesis. Non-coding RNAs (nc-RNAs) are endogenous molecules, and brain ischemia quickly changes the expression patterns of several non-coding RNA types, such as microRNA (miRNA/miR), long non-coding RNA (lncRNA), and circular RNA (circRNA). Furthermore, vascular endothelium-associated nc-RNAs are important mediators in the maintenance of healthy cerebrovascular function. In order to better understand how VECs are regulated epigenetically during an IS, in this review, we attempted to assemble the molecular functions of nc-RNAs that are linked with VECs during an IS.
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Affiliation(s)
- Zi-Lin Ren
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xiang-Dong Kang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yu-Xiao Zheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Han-Fen Shi
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Cong-Ai Chen
- Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100700, China
| | - Yu-Yu Shi
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Qing-Guo Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Fa-Feng Cheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Xue-Qian Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Chang-Xiang Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
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Feng X, Dong H, Li B, Yu L, Zhu J, Lou C, Zhang J. Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease. Front Genet 2023; 14:1050783. [PMID: 36793900 PMCID: PMC9923003 DOI: 10.3389/fgene.2023.1050783] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/09/2023] [Indexed: 01/31/2023] Open
Abstract
The pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) is implicated in airway inflammation, oxidative stress, protease/anti-protease and emphysema. Abnormally expressed non-coding RNAs (ncRNAs) play a vital role in regulation of COPD occurrence and progression. The regulatory mechanisms of the circRNA/lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) networks might facilitate our cognition of RNA interactions in COPD. This study aimed to identified novel RNA transcripts and constructed the potential ceRNA networks of COPD patients. Total transcriptome sequencing of the tissues from patients with COPD (COPD) (n = 7) and non-COPD control subjects (Normal) (n = 6) was performed, and the expression profiles of differentially expressed genes (DEGs), including mRNAs, lncRNAs, circRNAs, and miRNAs, were analyzed. The ceRNA network was established based on the miRcode and miRanda databases. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Gene set variation analysis (GSVA) were implemented for functional enrichment analysis of DEGs. Finally, CIBERSORTx was extracted to analyze the relevance between hub genes and various immune cells.The Starbase and JASPAR databases were used to construct hub-RNA binding proteins (RBPs) and lncRNA-transcription factor (TF) interaction networks. A total of 1,796 mRNAs, 2,207 lncRNAs, and 11 miRNAs showed differentially expression between the lung tissue samples from the normal and COPD groups. Based on these DEGs, lncRNA/circRNA-miRNA-mRNA ceRNA networks were constructed respectively. In addition, ten hub genes were identified. Among them, RPS11, RPL32, RPL5, and RPL27A were associated with the proliferation, differentiation, and apoptosis of the lung tissue. The biological function revealed that TNF-α via NF-kB and IL6/JAK/STAT3 signaling pathways were involved in COPD. Our research constructed the lncRNA/circRNA-miRNA-mRNA ceRNA networks, filtrated ten hub genes may regulate the TNF-α/NF-κB, IL6/JAK/STAT3 signally pathways, which indirectly elucidated the post-transcriptional regulation mechanism of COPD and lay the foundation for excavating the novel targets of diagnosis and treatment in COPD.
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Affiliation(s)
- Xueyan Feng
- Clinical medical school, Ningxia Medical University, Yinchuan, China
| | - Hui Dong
- Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Beibei Li
- Clinical medical school, Ningxia Medical University, Yinchuan, China
| | - Liang Yu
- Department of Thoracic Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Jinyuan Zhu
- Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Caili Lou
- Clinical medical school, Ningxia Medical University, Yinchuan, China
| | - Jin Zhang
- Department of Respiratory and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, China,*Correspondence: Jin Zhang,
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Yang L, Du H, Zhang X, Gao B, Zhang D, Qiao Z, Su X, Bao T, Han S. Circ VRK1/microRNA-17/PTEN axis modulates the angiogenesis of human brain microvascular endothelial cells to affect injury induced by oxygen-glucose deprivation/reperfusion. BMC Neurosci 2023; 24:8. [PMID: 36707796 PMCID: PMC9881374 DOI: 10.1186/s12868-023-00774-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/04/2023] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) can act as microRNA (miRNA) sponges, thus regulating gene expression. The role of circRNAs in the process of oxygen-glucose deprivation/reoxygenation (OGD/R) is unclear. Here, we explored the mechanism underlying Circ VRK1 in human brain microvascular endothelial cells (HBMVECs) injury induced by OGD/R. METHODS The OGD/R cell model was established in HBMVECs. The microarray was applied to detect differentially expressed circRNAs, followed by subcellular fractionation assay. Colony formation assay, flow cytometry, ELISA, tube formation, Transwell and western blot assays were performed for loss-of-function assay. HE staining, TTC staining, immunohistochemistry and western blot were performed in an established mouse model. The relationships between Circ VRK1 and miR-17, and between miR-17 and PTEN were detected by bioinformatics and dual-luciferase assays. Rescue experiments were conducted in vitro and in vivo, and PI3K/AKT activity was detected by Western Blot. RESULTS Circ VRK1, predominantly present in the cytoplasm of cells, was upregulated in the HBMVECs exposed to OGD/R. Circ VRK1 downregulation decreased proliferation, migration, tube formation, inflammatory factors and oxidative stress, while increased apoptosis in HBMVECs. Moreover, Circ VRK1 silencing reduced neurological damage, cerebral infarct size, CD34-positive cell counts and VEGF expression in mice. Circ VRK1 mediated PTEN expression and the PI3K/AKT pathway by targeting miR-17. Deletion of miR-17 inhibited the effects of Circ VRK1 siRNA, and silencing of PTEN suppressed the effects of miR-17 inhibitor. CONCLUSION Circ VRK1 was upregulated during OGD/R. Circ VRK1 downregulation regulates PTEN expression by targeting miR-17, thereby promoting PI3K/AKT pathway activity to alleviate OGD/R injury.
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Affiliation(s)
- Lei Yang
- Department of Neurosurgery, Shijiazhuang People’s Hospital, No.365, Jianhua South Road, Yuhua District, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Hong Du
- grid.452702.60000 0004 1804 3009Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Xuejing Zhang
- Center of Medical Research, Shijiazhuang People’s Hospital, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Bulang Gao
- Center of Medical Research, Shijiazhuang People’s Hospital, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Dongliang Zhang
- Department of Neurosurgery, Shijiazhuang People’s Hospital, No.365, Jianhua South Road, Yuhua District, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Zongrong Qiao
- Department of Neurosurgery, Shijiazhuang People’s Hospital, No.365, Jianhua South Road, Yuhua District, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Xianhui Su
- Department of Neurosurgery, Shijiazhuang People’s Hospital, No.365, Jianhua South Road, Yuhua District, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Tong Bao
- Department of Neurosurgery, Shijiazhuang People’s Hospital, No.365, Jianhua South Road, Yuhua District, Shijiazhuang, 050000 Hebei People’s Republic of China
| | - Siqin Han
- grid.256883.20000 0004 1760 8442Graduate School, Hebei Medical University, Shijiazhuang, 050017 Hebei People’s Republic of China
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21
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Erokhina TN, Ryazantsev DY, Zavriev SK, Morozov SY. Regulatory miPEP Open Reading Frames Contained in the Primary Transcripts of microRNAs. Int J Mol Sci 2023; 24:ijms24032114. [PMID: 36768436 PMCID: PMC9917039 DOI: 10.3390/ijms24032114] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/18/2023] [Accepted: 01/19/2023] [Indexed: 01/25/2023] Open
Abstract
This review aims to consider retrospectively the available data on the coding properties of pri-microRNAs and the regulatory functions of their open reading frames (ORFs) and the encoded peptides (miPEPs). Studies identifying miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed together with a brief description of the methods to identify pri-miRNA ORFs and the encoded protein products. Generally, miPEPs have been identified in many plant species of several families and in a few animal species. Importantly, molecular mechanisms of the miPEP action are often quite different between flowering plants and metazoan species. Requirement for the additional studies in these directions is highlighted by alternative findings concerning negative or positive regulation of pri-miRNA/miRNA expression by miPEPs in plants and animals. Additionally, the question of how miPEPs are distributed in non-flowering plant taxa is very important for understanding the evolutionary origin of such micropeptides. Evidently, further extensive studies are needed to explore the functions of miPEPs and the corresponding ORFs and to understand the full set of their roles in eukaryotic organisms. Thus, we address the most recent integrative views of different genomic, physiological, and molecular aspects concerning the expression of miPEPs and their possible fine functions.
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Affiliation(s)
- Tatiana N. Erokhina
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
| | - Dmitriy Y. Ryazantsev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
| | - Sergey K. Zavriev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
| | - Sergey Y. Morozov
- Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia
- Correspondence:
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22
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Liu J, Jiang M, Guan J, Wang Y, Yu W, Hu Y, Zhang X, Yang J. LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis. J Thorac Dis 2022; 14:4081-4095. [PMID: 36389338 PMCID: PMC9641317 DOI: 10.21037/jtd-22-1261] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/14/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND Lung cancer, especially lung squamous cell carcinoma (LUSC), is one of the most common malignant tumors worldwide. Currently, radiosensitization research is a vital direction for the improvement of LUSC therapy. Long non-coding RNAs (lncRNAs) can be novel biomarkers due to their multiple functions in cancers. However, the function and mechanism of lncRNA KCNQ1OT1 in the radioresistance of LUSC remain to be elucidated. METHODS The clonogenic assay was employed to determine the radioresistance of SK-MES-1R and NCI-H226R cells. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were conducted for the detection of gene expression. Cell proliferation was determined by the methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell apoptosis was assessed by flow cytometry. The relationships between genes were also evaluated by applying the luciferase reporter and radioimmunoprecipitation (RIP) assays. RESULTS Radioresistant LUSC cells (SK-MES-1R and NCI-H226R) had strong resistance to X-ray irradiation, and lncRNA KCNQ1OT1 was highly expressed in SK-MES-1R and NCI-H226R cells. Moreover, knockdown of lncRNA KCNQ1OT1 prominently suppressed proliferation, attenuated radioresistance, and accelerated the apoptosis of SK-MES-1R and NCI-H226R cells. More importantly, we verified that miR-491-5p was a regulatory target of lncRNA KCNQ1OT1, and Xenopus kinesin-like protein 2 (TPX2) and RING finger protein 2 (RNF2) were the target genes of miR-491-5p. The rescue experiment results also demonstrated that miR-491-5p was involved in the inhibition of cell proliferation and the downregulation of TPX2 and RNF2 expression mediated by lncRNA KCNQ1OT1 knockdown in SK-MES-1R and NCI-H226R cells. CONCLUSIONS LncRNA KCNQ1OT1 was associated with the radioresistance of radioresistant LUSC cells, and the lncRNA KCNQ1OT1/miR-491-5p/TPX2-RNF2 axis might be used as a therapeutic target to enhance the radiosensitivity of radioresistant LUSC cells.
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Affiliation(s)
- Jiahui Liu
- Department of Cardiothoracic Surgery Nursing Platform, First Hospital of Jilin University, Changchun, China
| | - Mi Jiang
- Department of Cardiothoracic Surgery Nursing Platform, First Hospital of Jilin University, Changchun, China
| | - Jinlei Guan
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuan Wang
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wenjuan Yu
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuanping Hu
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xin Zhang
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jie Yang
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Regulatory mechanisms and function of hypoxia-induced long noncoding RNA NDRG1-OT1 in breast cancer cells. Cell Death Dis 2022; 13:807. [PMID: 36127332 PMCID: PMC9489765 DOI: 10.1038/s41419-022-05253-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 09/06/2022] [Accepted: 09/09/2022] [Indexed: 01/23/2023]
Abstract
Hypoxia is a classic feature of the tumor microenvironment that has profound effects on cancer progression and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs), a component of the noncoding genome, have been increasingly investigated due to their diverse roles in tumorigenesis. Previously, a hypoxia-induced lncRNA, NDRG1-OT1, was identified in MCF-7 breast cancer cells using next-generation sequencing. However, the regulatory mechanisms of NDRG1-OT1 remain elusive. Therefore, the purpose of this study was to investigate the regulatory mechanisms and functional roles of NDRG1-OT1 in breast cancer cells. Expression profiling of NDRG1-OT1 revealed that it was upregulated under hypoxia in different breast cancer cells. Overexpression and knockdown of HIF-1α up- and downregulated NDRG1-OT1, respectively. Luciferase reporter assays and chromatin immunoprecipitation assays validated that HIF-1α transcriptionally activated NDRG1-OT1 by binding to its promoter (-1773 to -1769 and -647 to -643 bp). Next, to investigate whether NDRG1-OT1 could function as a miRNA sponge, results of in silico analysis, expression profiling of predicted miRNAs, and RNA immunoprecipitation assays indicated that NDRG1-OT1 could act as a miRNA sponge of miR-875-3p. In vitro and in vivo functional assays showed that NDRG1-OT1 could promote tumor growth and migration. Lastly, a small peptide (66 a.a.) translated from NDRG1-OT1 was identified. In summary, our findings revealed novel regulatory mechanisms of NDRG1-OT1 by HIF-1α and upon miR-875-3p. Also, NDRG1-OT1 promoted the malignancy of breast cancer cells and encoded a small peptide.
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24
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Zhou X, Du J. CircRNAs: novel therapeutic targets in multiple myeloma. Mol Biol Rep 2022; 49:10667-10676. [PMID: 35729478 DOI: 10.1007/s11033-022-07668-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/31/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Circular RNA (circRNA) is a type of non-coding RNA that has recently attracted the attention of researchers. Multiple myeloma (MM) is a hematological malignancy with a dismal prognosis that indicates a pressing need for better treatment alternatives, particularly in terms of biological indicators. According to recent research findings, the presence of circRNA is also closely related to the incidence and progression of malignant hemopathy. There have been, however, only a few investigations of circRNA in MM. MATERIAL AND METHODS This review will be on the biological properties and functions of circRNA in MM and a discussion of the clinical utility of circRNA in the diagnosis, prognosis, and treatment of MM. CONCLUSIONS CircRNA is involved in gene transcription, translation, and epigenetic modification as well as the regulation of cancer cell proliferation, invasion, and metastasis, and hence, promotes or inhibits the occurrence and progression of MM. Therefore, circRNA holds promise as a potential future MM biomarker.
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Affiliation(s)
- Xinyi Zhou
- Department of Hematology, Myeloma and Lymphoma Center, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu Area, Shanghai, 200003, China
| | - Juan Du
- Department of Hematology, Myeloma and Lymphoma Center, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu Area, Shanghai, 200003, China.
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25
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Cancer-related micropeptides encoded by ncRNAs: Promising drug targets and prognostic biomarkers. Cancer Lett 2022; 547:215723. [DOI: 10.1016/j.canlet.2022.215723] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/14/2022] [Accepted: 05/01/2022] [Indexed: 02/07/2023]
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Ribosome-Associated ncRNAs (rancRNAs) Adjust Translation and Shape Proteomes. Noncoding RNA 2022; 8:ncrna8020022. [PMID: 35314615 PMCID: PMC8938821 DOI: 10.3390/ncrna8020022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 12/02/2022] Open
Abstract
The regulation of protein synthesis is of extreme importance for cell survival in challenging environmental conditions. Modulating gene expression at the level of translation allows a swift and low-energy-cost response to external stimuli. In the last decade, an emerging class of regulatory ncRNAs, namely ribosome-associated non-coding RNAs (rancRNAs), has been discovered. These rancRNAs have proven to be efficient players in the regulation of translation as a first wave of stress adaptation by directly targeting the ribosome, the central enzyme of protein production. This underlying principle appears to be highly conserved, since rancRNAs are present in all three domains of life. Here, we review the major findings and mechanistic peculiarities of rancRNAs, a class of transcripts that is providing new and broader perspectives on the complexity of the ribosome and translation regulation.
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27
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Wang S, Zhong H, Ze R, Hong P, Li J, Tang X. Microarray analysis of lncRNA and mRNA expression profiles in patients with Legg-Calve-Perthes disease. Front Pediatr 2022; 10:974547. [PMID: 36160809 PMCID: PMC9490025 DOI: 10.3389/fped.2022.974547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The etiology and underlying pathogenic mechanisms of Legg-Calve-Perthes disease (LCPD) still remain unclear. A disruption of blood supply to the femoral head, producing ischemic necrosis, appears to be the critical pathological event. The lncRNAs play crucial roles in many biological processes and are dysregulated in various human diseases. However, its expression profiles and the potential regulatory roles in the development of LCPD have not been investigated. METHODS In this study, differentially expressed lncRNA and mRNA of Legg-Calve-Perthes disease patients were profiled. Several GO terms and pathways that play important roles in the regulation of vascular structure, function or coagulation were selected for further analysis. The lncRNA -mRNA interacting networks in LCPD tissues were constructed to identify novel potential targets for further investigation. RESULTS The microarray analysis revealed that 149 lncRNAs and 37 mRNAs were up-regulated, and 64 lncRNAs and 250 mRNAs were down-regulated in LCPD tissues. After filtering, we finally found 14 mRNAs and constructed an mRNA-lncRNA interacting network. Through the analysis of the interaction network, we finally found 13 differentially expressed lncRNAs, which may be implicated in the pathogenesis of LCPD. These mRNAs/lncRNAs were further validated with qRT-PCR. CONCLUSION The findings of this study established a co-expression network of disease-related lncRNAs and mRNAs which screened out from the concerned G.O. terms and Pathways, which may provide new sights for future studies on molecular mechanisms of LCPD.
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Affiliation(s)
- Shangyu Wang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haobo Zhong
- Department of Orthopedics, Huizhou First Hospital, Huizhou, China
| | - Renhao Ze
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Pan Hong
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin Li
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Tang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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28
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Mustafin RN. Relationship of Peptides and Long Non-Coding RNAs with Aging. ADVANCES IN GERONTOLOGY 2021. [DOI: 10.1134/s2079057021040081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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hsa_circ_0013401 Accelerates the Growth and Metastasis and Prevents Apoptosis and Autophagy of Neuroblastoma Cells by Sponging miR-195 to Release PAK2. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:9936154. [PMID: 34853631 PMCID: PMC8629642 DOI: 10.1155/2021/9936154] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 10/12/2021] [Accepted: 10/27/2021] [Indexed: 01/22/2023]
Abstract
Background Increased levels of circRNAs have been identified in a variety of cancers. However, the specific functions and mechanisms of circRNAs in neuroblastoma (NB) have not been fully explored. Methods The levels of hsa_circ_0045997, hsa_circ_0080307, hsa_circ_0013401, hsa_circ_0077578, and microRNA-195 were confirmed by RT-qPCR in NB. Gain- and loss-of-function assays and rescue experiments were conducted to determine the influence of hsa_circ_0013401, miR-195, and P21-activated kinase 2 (PAK2) on the proliferation, apoptosis, autophagy, migration, and invasion of NB cells. Regulatory gene targets were validated by the luciferase assay. A xenograft mouse model was used to determine the in vivo effects of hsa_circ_0013401. Results hsa_circ_0013401 was highly expressed, miR-195 was lowly expressed, and there was a negative correlation between hsa_circ_0013401 and miR-195 in NB. The inhibitory effects of hsa_circ_0013401 knockdown suppressed the proliferation, migration, and invasion and induced the apoptosis and autophagy of NB cells by targeting miR-195 to downregulate PAK2 expression. Luciferase reporter assays showed that miR-195 was a direct target of hsa_circ_0013401, and PAK2 was the downstream target gene of miR-195. In vivo studies showed that hsa_circ_0013401 promotes tumor formation. Conclusions hsa_circ_0013401 induced NB progression through miR-195 to enhance PAK2. Therefore, we might highlight a novel regulatory axis (hsa_circ_0013401/miR-195/PAK2) in NB.
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Cable J, Heard E, Hirose T, Prasanth KV, Chen LL, Henninger JE, Quinodoz SA, Spector DL, Diermeier SD, Porman AM, Kumar D, Feinberg MW, Shen X, Unfried JP, Johnson R, Chen CK, Wilusz JE, Lempradl A, McGeary SE, Wahba L, Pyle AM, Hargrove AE, Simon MD, Marcia M, Przanowska RK, Chang HY, Jaffrey SR, Contreras LM, Chen Q, Shi J, Mendell JT, He L, Song E, Rinn JL, Lalwani MK, Kalem MC, Chuong EB, Maquat LE, Liu X. Noncoding RNAs: biology and applications-a Keystone Symposia report. Ann N Y Acad Sci 2021; 1506:118-141. [PMID: 34791665 PMCID: PMC9808899 DOI: 10.1111/nyas.14713] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 10/06/2021] [Indexed: 01/07/2023]
Abstract
The human transcriptome contains many types of noncoding RNAs, which rival the number of protein-coding species. From long noncoding RNAs (lncRNAs) that are over 200 nucleotides long to piwi-interacting RNAs (piRNAs) of only 20 nucleotides, noncoding RNAs play important roles in regulating transcription, epigenetic modifications, translation, and cell signaling. Roles for noncoding RNAs in disease mechanisms are also being uncovered, and several species have been identified as potential drug targets. On May 11-14, 2021, the Keystone eSymposium "Noncoding RNAs: Biology and Applications" brought together researchers working in RNA biology, structure, and technologies to accelerate both the understanding of RNA basic biology and the translation of those findings into clinical applications.
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Affiliation(s)
| | - Edith Heard
- European Molecular Biology Laboratory (EMBL), Heidelberg, Heidelberg, Germany
- Collège de France, Paris, France
| | - Tetsuro Hirose
- Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
- Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
| | - Kannanganattu V Prasanth
- Department of Cell and Developmental Biology, Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Ling-Ling Chen
- State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Shanghai, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
- School of Life Sciences, Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences, Hangzhou, China
| | | | - Sofia A Quinodoz
- Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey
| | - David L Spector
- Cold Spring Harbor Laboratory, Cold Spring Harbor and Genetics Program, Stony Brook University, Stony Brook, New York
| | - Sarah D Diermeier
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | - Allison M Porman
- Biochemistry and Molecular Genetics Department, University of Colorado, Anschutz Medical Campus, Aurora, Colorado
| | - Dhiraj Kumar
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mark W Feinberg
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Xiaohua Shen
- Tsinghua-Peking Joint Center for Life Sciences, School of Medicine and School of Life Sciences, Tsinghua University, Beijing, China
| | - Juan Pablo Unfried
- Center for Applied Medical Research (CIMA), Department of Gene Therapy and Regulation of Gene Expression, Universidad de Navarra (UNAV), Pamplona, Spain
| | - Rory Johnson
- Department of Medical Oncology, Inselspital, Bern University Hospital; and Department for BioMedical Research University of Bern, Bern, Switzerland
- School of Biology and Environmental Science and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - Chun-Kan Chen
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, California
- Department of Genetics, Stanford University School of Medicine, Stanford, California
| | - Jeremy E Wilusz
- Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Adelheid Lempradl
- Department of Metabolism and Nutritional Programming, Van Andel Research Institute, Grand Rapids, Michigan
| | - Sean E McGeary
- Whitehead Institute for Biomedical Research, Cambridge, Massachusetts
- Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts
| | - Lamia Wahba
- Department of Genetics, Stanford University School of Medicine, Stanford, California
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Anna Marie Pyle
- Department of Genetics, Yale School of Medicine, New Haven, Connecticut
- Connecticut and Howard Hughes Medical Institute, Chevy Chase, Maryland
| | | | - Matthew D Simon
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut
| | - Marco Marcia
- European Molecular Biology Laboratory (EMBL) Grenoble, Grenoble, France
| | - Róża K Przanowska
- Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Howard Y Chang
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, California
- Howard Hughes Medical Institute, Stanford University, Stanford, California
| | - Samie R Jaffrey
- Department of Pharmacology, Weill Medical College of Cornell University, New York, New York
| | - Lydia M Contreras
- McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas
| | - Qi Chen
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, California
| | - Junchao Shi
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, California
| | - Joshua T Mendell
- Department of Molecular Biology, Harold C. Simmons Comprehensive Cancer Center, Hamon Center for Regenerative Science and Medicine; and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Lin He
- Division of Cellular and Developmental Biology, Molecular and Cell Biology Department, University of California at Berkeley, Berkeley, California
| | - Erwei Song
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center and Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Bioland Laboratory; Program of Molecular Medicine, Zhongshan School of Medicine, Sun Yat-sen University; and Fountain-Valley Institute for Life Sciences, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences Guangzhou, Guangzhou, China
| | - John L Rinn
- Department of Biochemistry, BioFrontiers Institute, and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado
| | - Mukesh Kumar Lalwani
- Queens Medical Research Institute, BHF Centre for Cardiovascular Sciences, University of Edinburgh, Scotland, United Kingdom
| | - Murat Can Kalem
- Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York
| | - Edward B Chuong
- Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado
| | - Lynne E Maquat
- Department of Biochemistry and Biophysics, School of Medicine and Dentistry and Center for RNA Biology, University of Rochester, Rochester, New York
| | - Xuhang Liu
- Laboratory of Systems Cancer Biology, The Rockefeller University, New York, New York
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Zhang H, Hao Y, Yang A, Xie L, Ding N, Xu L, Wang Y, Yang Y, Bai Y, Zhang H, Jiang Y. TGFB3-AS1 promotes Hcy-induced inflammation of macrophages via inhibiting the maturity of miR-144 and upregulating Rap1a. MOLECULAR THERAPY - NUCLEIC ACIDS 2021; 26:1318-1335. [PMID: 34853730 PMCID: PMC8609111 DOI: 10.1016/j.omtn.2021.10.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 08/23/2021] [Accepted: 10/28/2021] [Indexed: 11/23/2022]
Abstract
It has been demonstrated that homocysteine (Hcy) can cause inflammatory diseases. Long noncoding RNAs (lncRNA) and microRNAs (miRNAs) are involved in this biological process, but the mechanism underlying Hcy-induced inflammation remains poorly understood. Here, we found that lncRNA TGFB3-AS1 was highly expressed in macrophages treated with Hcy and the peripheral blood monocytes from cystathionine beta-synthase heterozygous knockout (CBS+/−) mice with a high-methionine diet using lncRNA microarray. In vivo and in vitro experiments further confirmed that TGFB3-AS1 accelerated Hcy-induced inflammation of macrophages through the Rap1a/wnt signaling pathway. Meanwhile, TGFB3-AS1 interacted with Rap1a and reduced degradation of Rap1a through inhibiting its ubiquitination in macrophages treated with Hcy. Rap1a mediated inflammation induced by Hcy and serves as a direct target of miR-144. Moreover, TGFB3-AS1 regulated miR-144 by binding to pri-miR-144 and inhibiting its maturation, which further regulated Rap1a expression. More importantly, we found that high expression of TGFB3-AS1 was positively correlated with the levels of Hcy and proinflammatory cytokines in serum of healthy individuals and patients with HHcy. Our study revealed a novel mechanism by which TGFB3-AS1 promoted inflammation of macrophages through inhibiting miR-144 maturation to stay miR-144 regulated inhibition of functional Rap1a expression.
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Affiliation(s)
- Hui Zhang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Yinju Hao
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Anning Yang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Lin Xie
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Ning Ding
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Lingbo Xu
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Yanhua Wang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
| | - Yong Yang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Department of Neurology, Region People's Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China
| | - Yongsheng Bai
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Department of Neurology, Region People's Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China
| | - Huiping Zhang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Corresponding author Huiping Zhang, Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, 804 Sheng Li Street, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.
| | - Yideng Jiang
- NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan 750004, Ningxia, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004 Ningxia, China
- Corresponding author Yideng Jiang, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Sheng Li Street, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.
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Chen CK, Cheng R, Demeter J, Chen J, Weingarten-Gabbay S, Jiang L, Snyder MP, Weissman JS, Segal E, Jackson PK, Chang HY. Structured elements drive extensive circular RNA translation. Mol Cell 2021; 81:4300-4318.e13. [PMID: 34437836 PMCID: PMC8567535 DOI: 10.1016/j.molcel.2021.07.042] [Citation(s) in RCA: 166] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 06/03/2021] [Accepted: 07/29/2021] [Indexed: 12/24/2022]
Abstract
The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.
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Affiliation(s)
- Chun-Kan Chen
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Departments of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Ran Cheng
- Baxter Laboratory, Department of Microbiology and Immunology and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Janos Demeter
- Baxter Laboratory, Department of Microbiology and Immunology and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Jin Chen
- Department of Pharmacology and Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Shira Weingarten-Gabbay
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Lihua Jiang
- Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Michael P Snyder
- Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Jonathan S Weissman
- Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Eran Segal
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Peter K Jackson
- Baxter Laboratory, Department of Microbiology and Immunology and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Howard Y Chang
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Departments of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
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Identification of tumor antigens with immunopeptidomics. Nat Biotechnol 2021; 40:175-188. [PMID: 34635837 DOI: 10.1038/s41587-021-01038-8] [Citation(s) in RCA: 128] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 07/29/2021] [Indexed: 12/18/2022]
Abstract
The identification of actionable tumor antigens is indispensable for the development of several cancer immunotherapies, including T cell receptor-transduced T cells and patient-specific mRNA or peptide vaccines. Most known tumor antigens have been identified through extensive molecular characterization and are considered canonical if they derive from protein-coding regions of the genome. By eluting human leukocyte antigen-bound peptides from tumors and subjecting these to mass spectrometry analysis, the peptides can be identified by matching the resulting spectra against reference databases. Recently, mass-spectrometry-based immunopeptidomics has enabled the discovery of noncanonical antigens-antigens derived from sequences outside protein-coding regions or generated by noncanonical antigen-processing mechanisms. Coupled with transcriptomics and ribosome profiling, this method enables the identification of thousands of noncanonical peptides, of which a substantial fraction may be detected exclusively in tumors. Spectral matching against the immense noncanonical reference may generate false positives. However, sensitive mass spectrometry, analytical validation and advanced bioinformatics solutions are expected to uncover the full landscape of presented antigens and clinically relevant targets.
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Suo RY, Wang ZY, Wang JS, Zhang GJ, Zhang J. Role of long non-coding RNA in regulating polarization of gastric cancer macrophages. Shijie Huaren Xiaohua Zazhi 2021; 29:1096-1101. [DOI: 10.11569/wcjd.v29.i19.1096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment. They are distributed in tumor tissues and distant metastatic sites, and are related to tumor progression and prognosis. TAMs M2 can promote tumor biological processes such as tumor proliferation, invasion, and metastasis, and inhibit apoptosis, and are obviously related to the poor prognosis of tumor patients. In recent years, the role of long non-coding RNAs (lncRNAs) in regulating the polarization of macrophages has gradually been revealed, which can affect the occurrence and development of tumors by adjusting the polarization of macrophages. Studies have shown that lncRNAs play an important role in the polarization process of gastric cancer macrophages. This article summarizes the related research reports, hoping to provide ideas for studies that interfere with the polarization process of TAMs to inhibit tumor progression.
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Affiliation(s)
- Rui-Yang Suo
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China,Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Zhi-Yu Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China,Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jian-Sheng Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Guang-Jian Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jia Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
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Li Y, Zhou H, Chen X, Zheng Y, Kang Q, Hao D, Zhang L, Song T, Luo H, Hao Y, Chen R, Zhang P, He S. SmProt: A Reliable Repository with Comprehensive Annotation of Small Proteins Identified from Ribosome Profiling. GENOMICS PROTEOMICS & BIOINFORMATICS 2021; 19:602-610. [PMID: 34536568 PMCID: PMC9039559 DOI: 10.1016/j.gpb.2021.09.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 12/30/2022]
Abstract
Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human microbiomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.
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Affiliation(s)
- Yanyan Li
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Honghong Zhou
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Xiaomin Chen
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yu Zheng
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Quan Kang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Di Hao
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Lili Zhang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Tingrui Song
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Huaxia Luo
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Yajing Hao
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Runsheng Chen
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Guangdong Geneway Decoding Bio-Tech Co. Ltd, Foshan 528316, China.
| | - Peng Zhang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
| | - Shunmin He
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
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Li X, Feng Y, Yang B, Xiao T, Ren H, Yu X, Li L, Li M, Zhang W. A novel circular RNA, hsa_circ_0030998 suppresses lung cancer tumorigenesis and Taxol resistance by sponging miR-558. Mol Oncol 2021; 15:2235-2248. [PMID: 33190405 PMCID: PMC8333779 DOI: 10.1002/1878-0261.12852] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 06/27/2020] [Accepted: 07/11/2020] [Indexed: 12/18/2022] Open
Abstract
Circular RNAs (circRNAs) are single-stranded RNAs which form a covalently closed continuous loop. Although originally shown to be non-protein-coding, some circRNAs can give rise to micropeptides. circRNAs have also been shown to play essential regulatory roles in a variety of developmental and disease processes. In a previous study, hsa_circ_0030998 was identified as a circRNA downregulated in lung cancer, but its potential implications and mechanisms in lung cancer were not addressed. Here, we showed that overexpressing circ_0030998 decreased proliferation, migration, and invasion of lung cancer cells, while also dampening resistance to Taxol, a classical antitumor drug. Depleting circ_0030998 reversed these phenotypic effects. A high circ_0030998 expression was correlated with a high survival rate in lung cancer patients. Additionally, we found circ_0030998 could downregulate miR-558 expression, serving as a microRNA sponge. In conclusion, our data support that hsa_circ_0030998 can slow down the progression of lung cancer by targeting miR-558 and suppress malignant phenotypes such as proliferation, migration, and invasion progression of lung cancer cells. Therefore, we highlight that circ_0030998 could be a novel tumor suppressor of lung cancer.
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Affiliation(s)
- Xiaoping Li
- Department of Thoracic SurgeryTianjin First Central HospitalChina
| | - Yiling Feng
- Department of Oncology Armed Police Characteristic Medical CenterTianjinChina
| | - Bo Yang
- Department of Thoracic SurgeryTianjin First Central HospitalChina
| | - Ting Xiao
- College of PharmacyState Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjinChina
| | - Haixia Ren
- Department of PharmacyTianjin First Central HospitalChina
| | - Xi Yu
- Department of RespiratoryTianjin First Central HospitalChina
| | - Lei Li
- Department of Thoracic SurgeryTianjin First Central HospitalChina
| | - Mingjiang Li
- Department of Thoracic SurgeryTianjin First Central HospitalChina
| | - Weidong Zhang
- Department of Thoracic SurgeryTianjin First Central HospitalChina
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Erokhina TN, Ryazantsev DY, Samokhvalova LV, Mozhaev AA, Orsa AN, Zavriev SK, Morozov SY. Activity of Chemically Synthesized Peptide Encoded by the miR156A Precursor and Conserved in the Brassicaceae Family Plants. BIOCHEMISTRY (MOSCOW) 2021; 86:551-562. [PMID: 33993858 DOI: 10.1134/s0006297921050047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
It was recently found that the primary transcripts of some microRNA genes (pri-miRNAs) are able to express peptides with 12 to 40 residues in length. These peptides, called miPEPs, participate in the transcriptional regulation of their own pri-miRNAs. In our previous studies, we used bioinformatic approach for comparative analysis of pri-miRNA sequences in plant genomes to identify a new group of miPEPs (miPEP-156a peptides) encoded by pri-miR156a in several dozen species of the Brassicaceae family. Exogenous miPEP-156a peptides could efficiently penetrate into the plant seedlings through the root system and spread systemically to the leaves. The peptides produced moderate morphological effect accelerating primary root growth. In parallel, the miPEP-156a peptides upregulated expression of their own pri-miR156a. Importantly, the observed effects at both morphological and molecular levels correlated with the peptide ability to quickly translocate into the cell nucleus and to bind chromatin. In this work, we established secondary structure of the miPEP-156a and demonstrated its changes induced by formation of the peptide complex with DNA.
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Affiliation(s)
- Tatiana N Erokhina
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Dmitry Yu Ryazantsev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Larisa V Samokhvalova
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Andrey A Mozhaev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Alexander N Orsa
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Sergey K Zavriev
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
| | - Sergey Yu Morozov
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
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He Y, Zhang H, Deng J, Cai Z, Gu M, Zhao C, Guo Y. The functions of fluoxetine and identification of fluoxetine-mediated circular RNAs and messenger RNAs in cerebral ischemic stroke. Bioengineered 2021; 12:2364-2376. [PMID: 34098829 PMCID: PMC8806530 DOI: 10.1080/21655979.2021.1935403] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Fluoxetine is used to improve cognition, exercise ability, depression, and neurological functions in patients with cerebral ischemic stroke. Circular RNAs (circRNAs) play important regulatory roles in multiple diseases. However, studies regarding the fluoxetine-mediated circRNA-microRNA-messenger RNA (mRNA) axis have not been conducted. This study is aim to investigate the functions of fluoxetine and identification of fluoxetine-mediated circRNAs and mRNAs in cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) rat models were successfully established at fisrt, and then rats were intraperitoneally injected with 10-mg/kg fluoxetine hydrochloride for 14 d. Afterward, the cerebral infarction area was evaluated using triphenyltetrazolium chloride staining. High-throughput sequencing was adopted to screen the differential circRNAs and mRNAs. The candidate circRNAs, mRNAs, and potential microRNAs were verified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addtion, microRNA and circRNA binding was verified using the dual-luciferase reporter assay. Results revealed that fluoxetine markedly diminished the cerebral infarction area in rats after MCAO. The circRNAs and mRNAs were differentially expressed, which includes 879 circRNAs and 815 mRNAs between sham and MCAO groups, respectively, and 958 circRNAs and 838 mRNAs between MCAO and fluoxetine groups, respectively. In which, circMap2k1 and Pidd1 expression was significantly increased in the MCAO group but suppressed after fluoxetine treatment. Moreover, circMap2k1 directly binds with miR-135b-5p. Taken together, we verified that fluoxetine could improve brain injury after cerebral ischemic stroke. Moreover, the circMap2k1/miR-135b-5p/Pidd1 axis is potentially involved in cerebral ischemic stroke.
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Affiliation(s)
- Yitao He
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Hui Zhang
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Jian Deng
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Zhili Cai
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Mei Gu
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Chenyong Zhao
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Yi Guo
- Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
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Vitorino R, Guedes S, Amado F, Santos M, Akimitsu N. The role of micropeptides in biology. Cell Mol Life Sci 2021; 78:3285-3298. [PMID: 33507325 PMCID: PMC11073438 DOI: 10.1007/s00018-020-03740-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 12/01/2020] [Accepted: 12/11/2020] [Indexed: 12/11/2022]
Abstract
Micropeptides are small polypeptides coded by small open-reading frames. Progress in computational biology and the analyses of large-scale transcriptomes and proteomes have revealed that mammalian genomes produce a large number of transcripts encoding micropeptides. Many of these have been previously annotated as long noncoding RNAs. The role of micropeptides in cellular homeostasis maintenance has been demonstrated. This review discusses different types of micropeptides as well as methods to identify them, such as computational approaches, ribosome profiling, and mass spectrometry.
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Affiliation(s)
- Rui Vitorino
- Departamento de Cirurgia E Fisiologia, Faculdade de Medicina da Universidade Do Porto, UnIC, Porto, Portugal.
- Department of Medical Sciences, iBiMED, University of Aveiro, Aveiro, Portugal.
| | - Sofia Guedes
- Departamento de Química, LAQV-REQUIMTE, Universidade de Aveiro, Aveiro, Portugal
- Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Francisco Amado
- Departamento de Química, LAQV-REQUIMTE, Universidade de Aveiro, Aveiro, Portugal
- Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Manuel Santos
- Department of Medical Sciences, iBiMED, University of Aveiro, Aveiro, Portugal
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He X, Xu T, Hu W, Tan Y, Wang D, Wang Y, Zhao C, Yi Y, Xiong M, Lv W, Wu M, Li X, Wu Y, Zhang Q. Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer. Front Cell Dev Biol 2021; 9:647736. [PMID: 33777954 PMCID: PMC7991790 DOI: 10.3389/fcell.2021.647736] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.
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Affiliation(s)
- Xiao He
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Xu
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weijie Hu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yufang Tan
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dawei Wang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yichen Wang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chongru Zhao
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Yi
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingchen Xiong
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenchang Lv
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Wu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xingrui Li
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiping Wu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Zhang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Geisinger A, Rodríguez-Casuriaga R, Benavente R. Transcriptomics of Meiosis in the Male Mouse. Front Cell Dev Biol 2021; 9:626020. [PMID: 33748111 PMCID: PMC7973102 DOI: 10.3389/fcell.2021.626020] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/15/2021] [Indexed: 12/18/2022] Open
Abstract
Molecular studies of meiosis in mammals have been long relegated due to some intrinsic obstacles, namely the impossibility to reproduce the process in vitro, and the difficulty to obtain highly pure isolated cells of the different meiotic stages. In the recent years, some technical advances, from the improvement of flow cytometry sorting protocols to single-cell RNAseq, are enabling to profile the transcriptome and its fluctuations along the meiotic process. In this mini-review we will outline the diverse methodological approaches that have been employed, and some of the main findings that have started to arise from these studies. As for practical reasons most studies have been carried out in males, and mostly using mouse as a model, our focus will be on murine male meiosis, although also including specific comments about humans. Particularly, we will center on the controversy about gene expression during early meiotic prophase; the widespread existing gap between transcription and translation in meiotic cells; the expression patterns and potential roles of meiotic long non-coding RNAs; and the visualization of meiotic sex chromosome inactivation from the RNAseq perspective.
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Affiliation(s)
- Adriana Geisinger
- Biochemistry-Molecular Biology, Facultad de Ciencias, Universidad de la República (UdelaR), Montevideo, Uruguay
- Department of Molecular Biology, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay
| | - Rosana Rodríguez-Casuriaga
- Department of Molecular Biology, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay
| | - Ricardo Benavente
- Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany
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Gómez-Gil V. Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review. Cancers (Basel) 2021; 13:379. [PMID: 33498521 PMCID: PMC7864190 DOI: 10.3390/cancers13030379] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 12/24/2022] Open
Abstract
Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGFβ, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGFβ, as a tumor suppressor or a tumor-promoter, together with its crosstalk with other signaling pathways, has hampered the development of safe and effective treatments aimed at halting the cancer progression. This systematic literature review aims to provide insight into the different approaches available to regulate TGFβ and/or the molecules involved in its synthesis, activation, or signaling, as a cancer treatment. The therapeutic strategies most commonly investigated include antisense oligonucleotides, which prevent TGFβ synthesis, to molecules that block the interaction between TGFβ and its signaling receptors, together with inhibitors of the TGFβ signaling cascade-effectors. The effectiveness and possible complications of the different potential therapies available are also discussed.
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Affiliation(s)
- Verónica Gómez-Gil
- Department of Biomedical Sciences (Area of Pharmacology), School of Medicine and Health Sciences, University of Alcalá, 28805 Alcalá de Henares, Madrid, Spain
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Zhang N, Wang X. Circular RNA ITCH mediates H 2O 2-induced myocardial cell apoptosis by targeting miR-17-5p via wnt/β-catenin signalling pathway. Int J Exp Pathol 2020; 102:22-31. [PMID: 33350543 PMCID: PMC7839958 DOI: 10.1111/iep.12367] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/16/2020] [Accepted: 06/28/2020] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular disease is a severe threat health worldwide, and circRNAs have been shown to be correlated with the development of cardiovascular disease. Expression of circ-ITCH and miR-17a-5p was evaluated by RT-qPCR. Cell viability was measured using CCK-8. Flow cytometry was applied to measure apoptosis rate. Binding between miR-17-5p and circ-ITCH was detected via luciferase reporter assays. Levels of ATP in cells were examined with ATP testing. Western blot was used to evaluate apoptosis-related proteins and proteins in Wnt/β-catenin signalling pathway. H2O2 induced apoptosis of H9c2 cells and lowered cell viability as well as ATP levels and circ-ITCH expression. After overexpression, circ-ITCH enhanced cell viability and ATP concentration. Meanwhile, apoptosis was inhibited. MiR-17-5p was the target of circ-ITCH as evidenced by luciferase report assays, with higher expression in H2O2-induced H9c2 cells. Knockdown of miR-17-5p could promote cell viability and level of ATP and curb apoptosis and p53 and PARP expression. Moreover, overexpressed miR-17-5p could reverse the function of upregulated circ-ITCH. Wnt3a, Wnt5a and β-catenin in Wnt/β-catenin signalling pathway were increased after H2O2 induction. Suppression of Wnt/β-catenin signalling pathway could initiate the process of injury in H9c2 cells. Circ-ITCH could protect myocardial cells from injuries caused by H2O2 by suppressing apoptosis while miR-17-5p played a reverse role, which could upregulate apoptosis and inhibit cell viability via Wnt/β-catenin signalling pathway.
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Affiliation(s)
- Nengfeng Zhang
- First Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsu ProvinceChina
- Cardiovascular DepartmentThe Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina
| | - Xu Wang
- First Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsu ProvinceChina
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Li Y, Yan J, Wang Y, Wang C, Zhang C, Li G. LINC00240 promotes gastric cancer cell proliferation, migration and EMT via the miR-124-3p / DNMT3B axis. Cell Biochem Funct 2020; 38:1079-1088. [PMID: 32526811 DOI: 10.1002/cbf.3551] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 04/02/2020] [Accepted: 05/03/2020] [Indexed: 01/17/2023]
Abstract
Gastric cancer (GC) remains one of prevalent causes of cancer-related deaths worldwide. Long noncoding RNA is related to various cancers. Our study was conducted to explore the biological effects of LINC00240 on the tumorigenesis of GC and uncover its possible mechanisms. LINC00240 expression was determined in GC cell lines and samples through quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The functional effects of LINC00240 were validated using in vitro and in vivo assays. Targets were assessed by AGO2-dependent RNA immunoprecipitation assay and dual-luciferase report assays. Our findings suggested higher LINC00240 expression in GC tissues and cells. Through downregulating LINC00240, cell proliferation, invasion and migration were retarded in vitro, and tumorigenesis of GC cells was notably suppressed in vivo. Further research showed that LINC00240 was a cytoplasmic lncRNA that shared miRNA response elements of microRNA (miR)-124-3p with DNMT3B, thus forming a LINC00240/miR-124-3p/DNMT3B axis explaining the functions of LINC00240. In a word, our study reveals that LINC00240 promotes GC tumorigenesis via a LINC00240/miR-124-3p/DNMT3B axis as an oncogene. These findings objectivise that LINC00240 may be a potential diagnostic biomarker for GC. SIGNIFICANCE OF THE STUDY: Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related death across the world. Then we analysed lncRNA microarray of GC and selected LINC00240 as the study object. Therefore, the potential molecular mechanism as well as physiological function of LINC00240 in GC was discussed. Then we reveal that LINC00240 acts as an oncogene in GC progression via the miR-99a-5p/IGF1R axis. This study is the first to demonstrate the roles of LINC00240 in GC.
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Affiliation(s)
- Yuanyuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jing Yan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yiting Wang
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Caifeng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Cheng Zhang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Guohua Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Zhang Z, Lin W, Lin Y, Kang M, Zhu J, Tong Z, Wu L, Sun J, Lin J. Long intergenic non-coding RNA Linc00485 promotes lung cancer progression by modulating miR-298/c-Myc axis. J Cell Mol Med 2020; 25:309-322. [PMID: 33237626 PMCID: PMC7810966 DOI: 10.1111/jcmm.16036] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 10/05/2020] [Accepted: 10/11/2020] [Indexed: 12/20/2022] Open
Abstract
Long non‐coding RNAs (lncRNAs), which are non‐protein‐coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer‐related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour‐node‐metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c‐Myc by directly binding to miR‐298; the effects of Linc00485 overexpression could be significantly reversed by a c‐Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down‐regulates miR‐298, resulting in the up‐regulation of c‐Myc and thereby promoting the development of lung cancer.
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Affiliation(s)
- Zhenyang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Wenwei Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Yuhan Lin
- School of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jiafu Zhu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Zhangwei Tong
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Long Wu
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jianhai Sun
- Department of Oncology, Hubei No. 3 People's Hospital of Jianghan University, Wuhan, Hebei, China
| | - Jiangbo Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Li J, Zhang X, Liu C. The computational approaches of lncRNA identification based on coding potential: Status quo and challenges. Comput Struct Biotechnol J 2020; 18:3666-3677. [PMID: 33304463 PMCID: PMC7710504 DOI: 10.1016/j.csbj.2020.11.030] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 11/15/2020] [Accepted: 11/16/2020] [Indexed: 12/13/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) make up a large proportion of transcriptome in eukaryotes, and have been revealed with many regulatory functions in various biological processes. When studying lncRNAs, the first step is to accurately and specifically distinguish them from the colossal transcriptome data with complicated composition, which contains mRNAs, lncRNAs, small RNAs and their primary transcripts. In the face of such a huge and progressively expanding transcriptome data, the in-silico approaches provide a practicable scheme for effectively and rapidly filtering out lncRNA targets, using machine learning and probability statistics. In this review, we mainly discussed the characteristics of algorithms and features on currently developed approaches. We also outlined the traits of some state-of-the-art tools for ease of operation. Finally, we pointed out the underlying challenges in lncRNA identification with the advent of new experimental data.
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Affiliation(s)
- Jing Li
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
- Center of Economic Botany, Core Botanical Gardens, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
| | - Xuan Zhang
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
| | - Changning Liu
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
- Center of Economic Botany, Core Botanical Gardens, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
- The Innovative Academy of Seed Design, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
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Yin H, Shen X, Zhao J, Cao X, He H, Han S, Chen Y, Cui C, Wei Y, Wang Y, Li D, Zhu Q. Circular RNA CircFAM188B Encodes a Protein That Regulates Proliferation and Differentiation of Chicken Skeletal Muscle Satellite Cells. Front Cell Dev Biol 2020; 8:522588. [PMID: 33240871 PMCID: PMC7677141 DOI: 10.3389/fcell.2020.522588] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 09/28/2020] [Indexed: 01/31/2023] Open
Abstract
Circular RNAs (circRNAs) are recognized as functional non-coding transcripts; however, emerging evidence has revealed that some synthetic circRNAs generate functional peptides or proteins. Additionally, the diverse biological functions of circRNAs include acting as miRNA-binding sponges, RNA-binding protein regulators, and protein translation templates. Previously, we found that circular RNA circFAM188B is a stable circular RNA and differentially expressed between broiler chickens and layers during embryonic skeletal muscle development. In this study, we found that circFAM188B exhibited a unique pattern of sharply decreased expression from embryonic day 10 (E10) to Day 35 (D35) after hatching. Our experimental results showed that circFAM188B promotes the proliferation, but inhibits the differentiation of chicken skeletal muscle satellite cells (SMSCs). Bioinformatic analysis revealed circFAM188B contain an opening reading frame (ORF) which translate into circFAM188B-103aa, internal ribosome entry site (IRES) analysis further confirmed the coding potential of circFAM188B. In addition, western blot assay detected a flag tagged circFAM188B-103aa, and several peptides of circFAM188B-103aa were detected by LC-MS/MS analysis. We further verified that the role of circFAM188B-103aa in chicken myogenesis is consistent with that of its parent transcript circFAM188B, which facilitates proliferation, but represses differentiation of chicken SMSC. Taken together, these results suggested that a novel protein circFAM188B-103aa encoded by circFAM188B that promotes the proliferation but inhibits the differentiation of chicken SMSCs.
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Affiliation(s)
- Huadong Yin
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xiaoxu Shen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jing Zhao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xinao Cao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Haorong He
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Shunshun Han
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yuqi Chen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Can Cui
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yuanhang Wei
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yan Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Diyan Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Qing Zhu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
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Qin Y, Yan G, Qiao Y, Wang D, Luo E, Hou J, Tang C. Emerging role of long non-coding RNAs in pulmonary hypertension and their molecular mechanisms (Review). Exp Ther Med 2020; 20:164. [PMID: 33093902 PMCID: PMC7571311 DOI: 10.3892/etm.2020.9293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 08/19/2020] [Indexed: 12/12/2022] Open
Abstract
Pulmonary hypertension (PH) is a life-threatening cardiopulmonary condition caused by several pathogenic factors. All types of PH are characterized by the excessive proliferation of pulmonary artery endothelial cells and pulmonary artery smooth muscle cells, apoptosis resistance, pulmonary vascular remodeling, sustained elevated pulmonary arterial pressure, right heart failure and even death. Over the past decade, next generation sequencing, particularly RNA-sequencing, has identified some long non-coding RNAs (lncRNAs) that may act as regulators of cell differentiation, proliferation and apoptosis. Studies have shown that lncRNAs are closely associated with the development of several diseases, including cardiovascular diseases. In addition, a number of studies have reported that lncRNAs, including maternally expressed gene 3, metastasis-associated lung adenocarcinoma transcript 1, taurine upregulated 1 and cancer susceptibility candidate 2, serve important roles in the pathogenesis of PH. Despite the development of novel drug treatments, the mortality rate of PH remains high with no evident downward trend. Therefore, certain lncRNAs may be considered as therapeutic targets for the treatment of incurable PH. The present review summarizes the latest research on lncRNAs and PH, aiming to briefly describe PH-associated lncRNAs and their mechanisms of action.
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Affiliation(s)
- Yuhan Qin
- Department of Cardiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Gaoliang Yan
- Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Yong Qiao
- Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Dong Wang
- Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Erfei Luo
- Department of Cardiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Jiantong Hou
- Department of Cardiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Chengchun Tang
- Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu 210009, P.R. China
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Teppan J, Barth DA, Prinz F, Jonas K, Pichler M, Klec C. Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis. Noncoding RNA 2020; 6:E42. [PMID: 32992718 PMCID: PMC7711482 DOI: 10.3390/ncrna6040042] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/21/2020] [Accepted: 09/23/2020] [Indexed: 12/30/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis. Angiogenesis, the formation of new blood vessels, is crucial for a tumor to receive sufficient amounts of nutrients and oxygen and therefore, to grow and exceed in its size over the diameter of 2 mm. In this review, the regulatory mechanisms of lncRNAs are described, which influence tumor angiogenesis by directly or indirectly regulating oncogenic pathways, interacting with other transcripts such as microRNAs (miRNAs) or modulating the tumor microenvironment. Further, angiogenic lncRNAs occurring in several cancer types such as liver, gastrointestinal cancer, or brain tumors are summarized. Growing evidence on the influence of lncRNAs on tumor angiogenesis verified these transcripts as potential predictive or diagnostic biomarkers or therapeutic targets of anti-angiogenesis treatment. However, there are many unsolved questions left which are pointed out in this review, hence driving comprehensive research in this area is necessary to enable an effective use of lncRNAs as either therapeutic molecules or diagnostic targets in cancer.
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Affiliation(s)
- Julia Teppan
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
| | - Dominik A. Barth
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
- Department of Experimental Therapeutics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Felix Prinz
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
| | - Katharina Jonas
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
| | - Martin Pichler
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
- Department of Experimental Therapeutics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Christiane Klec
- Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Internal Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; (J.T.); (D.A.B.); (F.P.); (K.J.); (C.K.)
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Dragomir MP, Manyam GC, Ott LF, Berland L, Knutsen E, Ivan C, Lipovich L, Broom BM, Calin GA. FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs. Noncoding RNA 2020; 6:E41. [PMID: 32977531 PMCID: PMC7712257 DOI: 10.3390/ncrna6040041] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/15/2020] [Accepted: 09/18/2020] [Indexed: 02/06/2023] Open
Abstract
Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually becoming appreciated as a new class of functional molecules that contribute to diverse cellular processes, and are deregulated in different diseases contributing to pathogenesis. As multiple publications have identified unique ncPEPs, we appreciated the need for assembling a new web resource that could gather information about these functional ncPEPs. We developed FuncPEP, a new database of functional ncRNA encoded peptides, containing all experimentally validated and functionally characterized ncPEPs. Currently, FuncPEP includes a comprehensive annotation of 112 functional ncPEPs and specific details regarding the ncRNA transcripts that encode these peptides. We believe that FuncPEP will serve as a platform for further deciphering the biologic significance and medical use of ncPEPs.
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Affiliation(s)
- Mihnea P. Dragomir
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
- Department of Surgery, Fundeni Clinical Hospital, Carol Davila University of Medicine and Pharmacy, 022328 Bucharest, Romania
| | - Ganiraju C. Manyam
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (G.C.M.); (B.M.B.)
| | - Leonie Florence Ott
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Léa Berland
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
| | - Erik Knutsen
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
- Department of Medical Biology, Faculty of Health Sciences, UiT—The Arctic University of Norway, N-9037 Tromsø, Norway
| | - Cristina Ivan
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Centre, Houston, TX 77054, USA
| | - Leonard Lipovich
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA;
| | - Bradley M. Broom
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (G.C.M.); (B.M.B.)
| | - George A. Calin
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (L.F.O.); (L.B.); (E.K.); (C.I.)
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Centre, Houston, TX 77054, USA
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