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Manjili DA, Babaei FN, Younesirad T, Ghadir S, Askari H, Daraei A. Dysregulated circular RNA and long non-coding RNA-Mediated regulatory competing endogenous RNA networks (ceRNETs) in ovarian and cervical cancers: A non-coding RNA-Mediated mechanism of chemotherapeutic resistance with new emerging clinical capacities. Arch Biochem Biophys 2025; 768:110389. [PMID: 40090441 DOI: 10.1016/j.abb.2025.110389] [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: 11/11/2024] [Revised: 03/01/2025] [Accepted: 03/13/2025] [Indexed: 03/18/2025]
Abstract
Cervical cancer (CC) and ovarian cancer (OC) are among the most common gynecological cancers with significant mortality in women, and their incidence is increasing. In addition to the prominent role of the malignant aspect of these cancers in cancer-related women deaths, chemotherapy drug resistance is a major factor that contributes to their mortality and presents a clinical obstacle. Although the exact mechanisms behind the chemoresistance in these cancers has not been revealed, accumulating evidence points to the dysregulation of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as key contributors. These ncRNAs perform the roles of regulators of signaling pathways linked to tumor formation and chemoresistance. Strong data from various recent studies have uncovered that the main mechanism of these ncRNAs in the induction of chemoresistance of CC and OC is done through a dysregulated miRNA sponge activity as competing endogenous RNA (ceRNA) in the competing endogenous RNA networks (ceRNETs), where a miRNA regulating a messenger RNA (mRNA) is trapped, thereby removing its inhibitory effect on the desired mRNA. Understanding these mechanisms is essential to enhancing treatment outcomes and managing the problem of drug resistance. This review provides a comprehensive overview of lncRNA- and circRNA-mediated ceRNETs as the core process of chemoresistance against the commonly used chemotherapeutics, including cisplatin, paclitaxel, oxaliplatin, carboplatin, and docetaxel in CC and OC. Furthermore, we highlight the clinical potential of these ncRNAs serving as diagnostic indicators of chemotherapy responses and therapeutic targets.
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Affiliation(s)
- Danial Amiri Manjili
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Fatemeh Naghdi Babaei
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Tayebeh Younesirad
- Department of Medical Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Sara Ghadir
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Hamid Askari
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Abdolreza Daraei
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Saadh MJ, Ehymayed HM, Alazzawi TS, Fahdil AA, Athab ZH, Yarmukhamedov B, Al-Anbari HHA, Shallal MM, Alsaikhan F, Farhood B. Role of circRNAs in regulating cell death in cancer: a comprehensive review. Cell Biochem Biophys 2025; 83:109-133. [PMID: 39243349 DOI: 10.1007/s12013-024-01492-6] [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] [Accepted: 08/21/2024] [Indexed: 09/09/2024]
Abstract
Despite multiple diagnostic and therapeutic advances, including surgery, radiation therapy, and chemotherapy, cancer preserved its spot as a global health concern. Prompt cancer diagnosis, treatment, and prognosis depend on the discovery of new biomarkers and therapeutic strategies. Circular RNAs (circRNAs) are considered as a stable, conserved, abundant, and varied group of RNA molecules that perform multiple roles such as gene regulation. There is evidence that circRNAs interact with RNA-binding proteins, especially capturing miRNAs. An extensive amount of research has presented the substantial contribution of circRNAs in various types of cancer. To fully understand the linkage between circRNAs and cancer growth as a consequence of various cell death processes, including autophagy, ferroptosis, and apoptosis, more research is necessary. The expression of circRNAs could be controlled to limit the occurrence and growth of cancer, providing a more encouraging method of cancer treatment. Consequently, it is critical to understand how circRNAs affect various forms of cancer cell death and evaluate whether circRNAs could be used as targets to induce tumor death and increase the efficacy of chemotherapy. The current study aims to review and comprehend the effects that circular RNAs exert on cell apoptosis, autophagy, and ferroptosis in cancer to investigate potential cancer treatment targets.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | - Tuqa S Alazzawi
- College of dentist, National University of Science and Technology, Dhi Qar, Iraq
| | - Ali A Fahdil
- Medical technical college, Al-Farahidi University, Baghdad, Iraq
| | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Bekhzod Yarmukhamedov
- Department of Surgical Dentistry and Dental Implantology, Tashkent State Dental Institute, Tashkent, Uzbekistan
- Department of Scientific affairs, Samarkand State Medical University, Samarkand, Uzbekistan
| | | | | | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
- School of Pharmacy, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia.
| | - Bagher Farhood
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Li D, Peng M, Zhou J. Noncoding RNA Linc00475 promotes the proliferation of colorectal cancer cells by targeting miR-107/CDK6 axis. J Biochem Mol Toxicol 2024; 38:e70012. [PMID: 39434447 DOI: 10.1002/jbt.70012] [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: 08/02/2024] [Revised: 09/11/2024] [Accepted: 10/02/2024] [Indexed: 10/23/2024]
Abstract
Colorectal cancer (CRC) represents a substantial challenge to public health. Despite extensive research, the pathogenesis of CRC is not yet fully elucidated, hindering the development of effective therapeutic strategies. Recent advancements have underscored the importance of Non-coding RNAs in tumor biology. Our research identified a significant upregulation of Linc00475 in CRC, which correlated with reduced survival rates among CRC patients. Consequently, this study aimed to elucidate the mechanisms by which Linc00475 contributed to CRC progression. Employing a comprehensive array of experimental techniques-including CCK-8 assays, colony formation assays, flow cytometry, quantitative PCR (qPCR), western blot analysis, and in vivo tumorigenesis assays-we have demonstrated that Linc00475 enhances CRC cell proliferation. Further analysis revealed that Linc00475 directly interacted with miR-107, leading to its downregulation. Moreover, our findings confirmed that miR-107 directly targeted CDK6, which was markedly downregulated following Linc00475 silencing. In vivo experiments further indicated that the silencing of Linc00475 markedly inhibited the proliferation of CRC cells. Collectively, our findings suggested that Linc00475 facilitated CRC cell proliferation through the regulation of the miR-107/CDK6 axis, thereby providing a novel perspective for understanding the molecular mechanisms underlying CRC development.
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Affiliation(s)
- Dongqing Li
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
- The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China
| | - Mingya Peng
- Nuclear Medicine Department, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China
| | - Juying Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Sharma A, Bansal C, Sharma KL, Kumar A. Circular RNA: The evolving potential in the disease world. World J Med Genet 2024; 12:93011. [DOI: 10.5496/wjmg.v12.i1.93011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/23/2024] [Accepted: 07/02/2024] [Indexed: 09/19/2024] Open
Abstract
Circular RNAs (circRNAs), a new star of noncoding RNAs, are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome. Most circRNAs are conserved throughout species and frequently show stage-specific expression during various stages of tissue development. CircRNAs were a mystery discovery, as they were initially believed to be a product of splicing errors; however, subsequent research has shown that circRNAs can perform various functions and help in the regulation of splicing and transcription, including playing a role as microRNA (miRNA) sponges. With the application of high throughput next-generation technologies, circRNA hotspots were discovered. There are emerging indications that explain the association of circRNAs with human diseases, like cancers, developmental disorders, and inflammation, and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases, including cancer. After the discoveries of miRNAs and long noncoding RNAs, circRNAs are now acting as a novel research entity of interest in the field of RNA disease biology. In this review, we aim to focus on major updates on the biogeny and metabolism of circRNAs, along with their possible/established roles in major human diseases.
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Affiliation(s)
- Aarti Sharma
- Department of Research, Mayo Clinic Arizona, Phoenix, AZ 85054, United States
| | - Cherry Bansal
- Department of Pathology, Dr. S Tantia Medical College, Hospital and Research Center, Sri Ganganagar 335002, Rajasthan, India
| | - Kiran Lata Sharma
- Department of Pathology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Dai Q, Liu Y, Ding F, Guo R, Cheng G, Wang H. CircRNAs: A promising target for intervention regarding glycolysis in gastric cancer. Heliyon 2024; 10:e34658. [PMID: 39816354 PMCID: PMC11734058 DOI: 10.1016/j.heliyon.2024.e34658] [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: 01/26/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 01/18/2025] Open
Abstract
Gastric cancer is characterized by a high incidence and mortality rate, with therapeutic efficacy currently constrained by substantial limitations. Aerobic glycolysis in cancer constitutes a pivotal aspect of the reprogramming of energy metabolism in tumor cells and profoundly influences the malignant progression of cancer. CircRNAs, serving as stable endogenous RNA, have been shown to regulate downstream targets by sponging miRNAs, which in turn are involved in the regulation of multiple malignant behaviors in a variety of cancers through the CircRNA-miRNA axis, suggesting that CircRNAs could be used as potential therapeutic targets for cancer. In recent years, it has been shown that some CircRNAs can be involved in the regulation of GC glycolysis, therefore, this paper summarizes the notable roles of some important CircRNAs in the regulation of GC glycolysis in recent years, which may be useful for our understanding of GC progression and the development of new therapeutic strategies.
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Affiliation(s)
- Qian Dai
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Yulin Liu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Fanghui Ding
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Rong Guo
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Gang Cheng
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Hua Wang
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
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Farazi MM, Jafarinejad-Farsangi S, Miri Karam Z, Gholizadeh M, Hadadi M, Yari A. Circular RNAs: Epigenetic regulators of PTEN expression and function in cancer. Gene 2024; 916:148442. [PMID: 38582262 DOI: 10.1016/j.gene.2024.148442] [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: 12/29/2023] [Revised: 03/04/2024] [Accepted: 04/03/2024] [Indexed: 04/08/2024]
Abstract
Epigenetic regulation of gene expression, without altering the DNA sequence, is involved in many normal cellular growth and division events, as well as diseases such as cancer. Epigenetics is no longer limited to DNA methylation, and histone modification, but regulatory non-coding RNAs (ncRNAs) also play an important role in epigenetics. Circular RNAs (circRNAs), single-stranded RNAs without 3' and 5' ends, have recently emerged as a class of ncRNAs that regulate gene expression. CircRNAs regulate phosphatase and tensin homolog (PTEN) expression at various levels of transcription, post-transcription, translation, and post-translation under their own regulation. Given the importance of PTEN as a tumor suppressor in cancer that inhibits one of the most important cancer pathways PI3K/AKT involved in tumor cell proliferation and survival, significant studies have been conducted on the regulatory role of circRNAs in relation to PTEN. These studies will be reviewed in this paper to better understand the function of this protein in cancer and explore new therapeutic approaches.
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Affiliation(s)
| | - Saeideh Jafarinejad-Farsangi
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | - Zahra Miri Karam
- Department of Medical Genetics, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Endocrinology & Metabolism Research Center, Institute of Basic & Clinical Physiology Sciences, Kerman University of Medical Sciences Kerman, Iran
| | - Maryam Gholizadeh
- Institute of Bioinformatics, University of Medicine Greifswald, Greifwald, Germany
| | - Maryam Hadadi
- Cardiovascular Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Abolfazl Yari
- Endocrinology & Metabolism Research Center, Institute of Basic & Clinical Physiology Sciences, Kerman University of Medical Sciences Kerman, Iran; Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
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Cheng Y, Shi R, Ben S, Chen S, Li S, Xin J, Wang M, Cheng G. Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing. J Biomed Res 2024; 38:358-368. [PMID: 38808547 PMCID: PMC11300518 DOI: 10.7555/jbr.38.20240030] [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: 02/02/2024] [Revised: 04/24/2024] [Accepted: 04/30/2024] [Indexed: 05/30/2024] Open
Abstract
The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer (PCa) as well as to elucidate biological mechanisms underlying the associations. We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify risk-associated circRNAs by using the MiOncoCirc database. We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls, and identified circHIBADH rs11973492 T>C as a significant risk-associated variant (odds ratio = 1.20, 95% confidence interval: 1.08-1.34, P = 7.06 × 10 -4) in a dominant genetic model, which altered the secondary structure of the corresponding RNA chain. In the in silico analysis, we found that circHIBADH sponged and silenced 21 RNA-binding proteins (RBPs) enriched in the RNA splicing pathway, among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house (four tissue samples) and publicly available single-cell transcriptomes. Additionally, we demonstrated that HNRNPA1 influenced hallmarks including MYC target, DNA repair, and E2F target signaling pathways, thereby promoting carcinogenesis. In conclusion, genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1, playing an oncogenic role in PCa.
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Affiliation(s)
- Yifei Cheng
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Rongjie Shi
- Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Shuai Ben
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Silu Chen
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Shuwei Li
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Junyi Xin
- Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Meilin Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, China
- The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215002, China
| | - Gong Cheng
- Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Yun C, Wang Y, Wang D, Zang J, Lv Z, Liu R, Cong H. CircABCB10 Promotes the Apoptosis and Inflammatory Response of 16HBE Cells by Cigarette Smoke Extract by Targeting miR-130a/PTEN Axis. IRANIAN JOURNAL OF PUBLIC HEALTH 2024; 53:592-604. [PMID: 38919307 PMCID: PMC11194655 DOI: 10.18502/ijph.v53i3.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/19/2023] [Indexed: 06/27/2024]
Abstract
Background Chronic obstructive pulmonary disease (COPD) has become a global public health problem due to its high mortality. So there is an urgent need to find an effective treatment. Methods The targeting relationship among circABCB10, miR-130a and PTEN was predicted by the targetscan database (TargetScanHuman 8.0, https://www.targetscan.org/vert_80/). A total of 60 patients which were from the second affiliated hospital of Qiqihar Medical University from 2022 to 2023 were enrolled. The lung condition was detected by CT (Computed Tomography). The expression levels of circABCB10, miR-130a and PTEN in lung tissues were determined by qRT-PCR. The COPD model was established by stimulating normal and silenced 16HBE cells in circABCB10 genes with cigarette smoke extract (CSE) at different concentrations. qRT-PCR was conducted for the expression levels of circABCB10, miR-130a and PTEN, WB for the expression levels of apoptotic proteins, ELISA for the content of inflammatory factors, and CCK8 for the effect of CSE on the proliferation of cells. Results CircABCB10 expression increased in lung tissues from patients with COPD and in 16HBE cells treated with CSE. The stimulation on cells with CSE increased the expression of inflammatory factors, while knocking down circABCB10 could reverse this response. The inflammatory response to the knockdown of circABCB10 was reversed by miR-130a inhibitor, which increased the expression of c-caspase 3. The targetscan database predicted the target factor downstream miR-130a was PTEN. Transfecting OE-PTEN reversed the inflammation of knocking down circABCB10, and increased the apoptosis and inflammation. Conclusion CircABCB10 can cause the inflammatory response by targeting miR-130a/PTEN axis, which is a mechanism that may lead to the occurrence and development of COPD.
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Affiliation(s)
- Changping Yun
- Department of Respiration, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
| | - Yuguang Wang
- CT Room, the Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
| | - Dongxu Wang
- CT Room, the Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
| | - Jialin Zang
- CT Room, the Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
| | - Zhen Lv
- School of Pharmacy, Qiqihar Medical University, Qiqihar 161000, China
| | - Ruinan Liu
- CT Room, the Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
| | - Houyi Cong
- CT Room, the Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China
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Travis G, McGowan EM, Simpson AM, Marsh DJ, Nassif NT. PTEN, PTENP1, microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics. Cancers (Basel) 2023; 15:4954. [PMID: 37894321 PMCID: PMC10605164 DOI: 10.3390/cancers15204954] [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: 09/11/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels. PTENP1, the processed pseudogene of PTEN, is an important transcriptional and post-transcriptional regulator of PTEN. PTENP1 expression produces sense and antisense transcripts modulating PTEN expression, in conjunction with miRNAs. Due to the high sequence similarity between PTEN and the PTENP1 sense transcript, the transcripts possess common miRNA binding sites with the potential for PTENP1 to compete for the binding, or 'sponging', of miRNAs that would otherwise target the PTEN transcript. PTENP1 therefore acts as a competitive endogenous RNA (ceRNA), competing with PTEN for the binding of specific miRNAs to alter the abundance of PTEN. Transcription from the antisense strand produces two functionally independent isoforms (PTENP1-AS-α and PTENP1-AS-β), which can regulate PTEN transcription. In this review, we provide an overview of the post-transcriptional regulation of PTEN through interaction with its pseudogene, the cellular miRNA milieu and operation of the ceRNA network. Furthermore, its importance in maintaining cellular integrity and how disruption of this PTEN-miRNA-PTENP1 axis may lead to cancer but also provide novel therapeutic opportunities, is discussed. Precision targeting of PTENP1-miRNA mediated regulation of PTEN may present as a viable alternative therapy.
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Affiliation(s)
- Glena Travis
- Cancer Biology, Faculty of Science, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia; (G.T.); (E.M.M.)
| | - Eileen M. McGowan
- Cancer Biology, Faculty of Science, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia; (G.T.); (E.M.M.)
- Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
| | - Ann M. Simpson
- Gene Therapy and Translational Molecular Analysis Laboratory, Faculty of Science, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia;
| | - Deborah J. Marsh
- Translational Oncology Group, Faculty of Science, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia;
| | - Najah T. Nassif
- Cancer Biology, Faculty of Science, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia; (G.T.); (E.M.M.)
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Chen W, Liu Y, Li L, Liang B, Wang S, Xu X, Xing D, Wu X. The potential role and mechanism of circRNAs in foam cell formation. Noncoding RNA Res 2023; 8:315-325. [PMID: 37032721 PMCID: PMC10074414 DOI: 10.1016/j.ncrna.2023.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/02/2023] [Accepted: 03/18/2023] [Indexed: 03/29/2023] Open
Abstract
Atherosclerosis is a significant risk factor for coronary heart disease (CHD) and myocardial infarction (MI). Atherosclerosis develops during foam cell generation, which is caused by an imbalance in cholesterol uptake, esterification, and efflux. LOX-1, SR-A1, and CD36 all increased cholesterol uptake. ACAT1 and ACAT2 promote free cholesterol (FC) esterification to cholesteryl esters (CE). The hydrolysis of CE to FC was aided by nCEH. FC efflux was promoted by ABCA1, ABCG1, ADAM10, and apoA-I. SR-BI promotes not only cholesterol uptake but also FC efflux. Circular RNAs (circRNAs), which are single-stranded RNAs with a closed covalent circular structure, have emerged as promising biomarkers and therapeutic targets for atherosclerosis due to their highly tissue, cell, and disease state-specific expression profiles. Numerous studies have shown that circRNAs regulate foam cell formation, acting as miRNA sponges to influence atherosclerosis development by regulating the expression of SR-A1, CD36, ACAT2, ABCA1, ABCG1, ADAM10, apoA-I, SR-B1. Several circRNAs, including circ-Wdr91, circ 0004104, circRNA0044073, circRNA_0001805, circDENND1B, circRSF1, circ 0001445, and circRNA 102682, are potential biomarkers for atherosclerosis to better evaluate cardiovascular risk. It is difficult to deliver synthetic therapeutic circRNAs to the desired target tissues. Nanotechnology, such as GA-RM/GZ/PL, may be an important solution to this problem. In this review, we focus on the potential role and mechanism of circRNA/miRNA axis in foam cell formation in the hopes of discovering new targets for the diagnosis, prevention, and treatment of atherosclerosis.
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Affiliation(s)
- Wujun Chen
- Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China
| | - Yihui Liu
- Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Key Laboratory of Precision Radiation Therapy for Tumors in Weifang City, School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261031, China
| | - Ling Li
- Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, China
| | - Bing Liang
- Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China
| | - Shuai Wang
- Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Key Laboratory of Precision Radiation Therapy for Tumors in Weifang City, School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261031, China
| | - Xiaodan Xu
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
- Corresponding author.
| | - Dongming Xing
- Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China
- School of Life Sciences, Tsinghua University, Beijing, 100084, China
- Corresponding author. Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China.
| | - Xiaolin Wu
- Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China
- Corresponding author. Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China.
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Gabryelska MM, Conn SJ. The RNA interactome in the Hallmarks of Cancer. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 14:e1786. [PMID: 37042179 PMCID: PMC10909452 DOI: 10.1002/wrna.1786] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/12/2023] [Accepted: 03/20/2023] [Indexed: 04/13/2023]
Abstract
Ribonucleic acid (RNA) molecules are indispensable for cellular homeostasis in healthy and malignant cells. However, the functions of RNA extend well beyond that of a protein-coding template. Rather, both coding and non-coding RNA molecules function through critical interactions with a plethora of cellular molecules, including other RNAs, DNA, and proteins. Deconvoluting this RNA interactome, including the interacting partners, the nature of the interaction, and dynamic changes of these interactions in malignancies has yielded fundamental advances in knowledge and are emerging as a novel therapeutic strategy in cancer. Here, we present an RNA-centric review of recent advances in the field of RNA-RNA, RNA-protein, and RNA-DNA interactomic network analysis and their impact across the Hallmarks of Cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
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Affiliation(s)
- Marta M Gabryelska
- Flinders Health and Medical Research Institute (FHMRI), College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - Simon J Conn
- Flinders Health and Medical Research Institute (FHMRI), College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
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12
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Gu A, Jaijyan DK, Yang S, Zeng M, Pei S, Zhu H. Functions of Circular RNA in Human Diseases and Illnesses. Noncoding RNA 2023; 9:38. [PMID: 37489458 PMCID: PMC10366867 DOI: 10.3390/ncrna9040038] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/23/2023] [Accepted: 06/28/2023] [Indexed: 07/26/2023] Open
Abstract
Circular RNAs (circRNAs) represent single-stranded RNA species that contain covalently closed 3' and 5' ends that provide them more stability than linear RNA, which has free ends. Emerging evidence indicates that circRNAs perform essential functions in many DNA viruses, including coronaviruses, Epstein-Barr viruses, cytomegalovirus, and Kaposi sarcoma viruses. Recent studies have confirmed that circRNAs are present in viruses, including DNA and RNA viruses, and play various important functions such as evading host immune response, disease pathogenesis, protein translation, miRNA sponges, regulating cell proliferation, and virus replication. Studies have confirmed that circRNAs can be biological signatures or pathological markers for autoimmune diseases, neurological diseases, and cancers. However, our understanding of circRNAs in DNA and RNA viruses is still limited, and functional evaluation of viral and host circRNAs is essential to completely understand their biological functions. In the present review, we describe the metabolism and cellular roles of circRNA, including its roles in various diseases and viral and cellular circRNA functions. Circular RNAs are found to interact with RNA, proteins, and DNA, and thus can modulate cellular processes, including translation, transcription, splicing, and other functions. Circular RNAs interfere with various signaling pathways and take part in vital functions in various biological, physiological, cellular, and pathophysiological processes. We also summarize recent evidence demonstrating cellular and viral circRNA's roles in DNA and RNA viruses in this growing field of research.
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Affiliation(s)
- Alison Gu
- Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
| | - Dabbu Kumar Jaijyan
- Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
| | - Shaomin Yang
- Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518052, China
| | - Mulan Zeng
- Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
| | - Shaokai Pei
- Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
| | - Hua Zhu
- Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
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13
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Lichołai S, Studzińska D, Plutecka H, Gubała T, Sanak M. Comprehensive Analysis of Circular RNAs in Endothelial Cells. Int J Mol Sci 2023; 24:10025. [PMID: 37373172 DOI: 10.3390/ijms241210025] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/29/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Non-coding RNAs constitute a heterogeneous group of molecules that lack the ability to encode proteins but retain the potential ability to influence cellular processes through a regulatory mechanism. Of these proteins, microRNAs, long non-coding RNAs, and more recently, circular RNAs have been the most extensively described. However, it is not entirely clear how these molecules interact with each other. For circular RNAs, the basics of their biogenesis and properties are also lacking. Therefore, in this study we performed a comprehensive analysis of circular RNAs in relation to endothelial cells. We identified the pool of circular RNAs present in the endothelium and showed their spectrum and expression across the genome. Using different computational strategies, we proposed approaches to search for potentially functional molecules. In addition, using data from an in vitro model that mimics conditions in the endothelium of an aortic aneurysm, we demonstrated altered expression levels of circRNAs mediated by microRNAs.
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Affiliation(s)
- Sabina Lichołai
- Division of Molecular Biology and Clinical Genetics, Faculty of Medicine, Jagiellonian University Medical College, 31-066 Krakow, Poland
| | - Dorota Studzińska
- Department of Intensive Care and Perioperative Medicine, Faculty of Medicine, Jagiellonian University Medical College, 31-901 Krakow, Poland
| | - Hanna Plutecka
- Division of Molecular Biology and Clinical Genetics, Faculty of Medicine, Jagiellonian University Medical College, 31-066 Krakow, Poland
| | - Tomasz Gubała
- Sano-Centre for Computational Medicine, 30-072 Krakow, Poland
| | - Marek Sanak
- Division of Molecular Biology and Clinical Genetics, Faculty of Medicine, Jagiellonian University Medical College, 31-066 Krakow, Poland
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14
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Hu Q, Li Z, Li Y, Deng X, Chen Y, Ma X, Zeng J, Zhao Y. Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives. Phytother Res 2023. [PMID: 37157181 DOI: 10.1002/ptr.7866] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/17/2023] [Accepted: 04/25/2023] [Indexed: 05/10/2023]
Abstract
Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.
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Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Zhibei Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yubing Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinyu Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
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15
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Castro-Muñoz LJ, Vázquez Ulloa E, Sahlgren C, Lizano M, De La Cruz-Hernández E, Contreras-Paredes A. Modulating epigenetic modifications for cancer therapy (Review). Oncol Rep 2023; 49:59. [PMID: 36799181 PMCID: PMC9942256 DOI: 10.3892/or.2023.8496] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/08/2022] [Indexed: 02/12/2023] Open
Abstract
Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA‑based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer.
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Affiliation(s)
| | - Elenaé Vázquez Ulloa
- Faculty of Science and Engineering/Cell Biology, University of Turku and Åbo Akademi University, Turku 20500, Finland
- Turku Bioscience, University of Turku and Åbo Akademi University, Turku 20500, Finland
| | - Cecilia Sahlgren
- Faculty of Science and Engineering/Cell Biology, University of Turku and Åbo Akademi University, Turku 20500, Finland
- Turku Bioscience, University of Turku and Åbo Akademi University, Turku 20500, Finland
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands
- Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands
| | - Marcela Lizano
- Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerología-Universidad Nacional Autonoma de Mexico, Ciudad de Mexico 14080, Mexico
- Departamento de Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico 04510, Mexico
| | - Erick De La Cruz-Hernández
- Laboratory of Research in Metabolic and Infectious Diseases, Multidisciplinary Academic Division of Comalcalco, Juarez Autonomous University of Tabasco, Comalcalco, Tabasco 86650, Mexico
| | - Adriana Contreras-Paredes
- Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerología-Universidad Nacional Autonoma de Mexico, Ciudad de Mexico 14080, Mexico
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16
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Wang J, Zheng L, Hu C, Kong D, Zhou Z, Wu B, Wu S, Fei F, Shen Y. CircZFR promotes pancreatic cancer progression through a novel circRNA-miRNA-mRNA pathway and stabilizing epithelial-mesenchymal transition protein. Cell Signal 2023; 107:110661. [PMID: 36990335 DOI: 10.1016/j.cellsig.2023.110661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 03/09/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023]
Abstract
Pancreatic cancer (PC) ranks third in incidence and seventh in mortality among cancers worldwide. CircZFR has been implicated in various human cancers. Yet, how they affect PC progression is understudied. Herein, we demonstrated that circZFR was upregulated in PC tissues and cells, a feature that was correlated with the poor performance of patients with PC. Functional analyses elucidated that circZFR facilitated cell proliferation and enhanced tumorigenicity of PC. Moreover, we found that circZFR facilitated cell metastasis by differentially regulating the levels of proteins related to epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that circZFR sponged miR-375, thereby upregulating the downstream target gene, GREMLIN2 (GREM2). Additionally, circZFR knockdown resulted in attenuation of the JNK pathway, an effect that was reversed by GREM2 overexpression. Collectively, our findings implicate circZFR as a positive regulator of PC progression through the miR-375/GREM2/JNK axis.
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Affiliation(s)
- Jing Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Liping Zheng
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Chundong Hu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Demiao Kong
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, No. 83 EastZhongshan Road, Nanming District, Guiyang, Guizhou 550001, China
| | - Zhongcheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Bin Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Shaohan Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Famin Fei
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China.
| | - Yiyu Shen
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China.
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17
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Dawoud A, Ihab Zakaria Z, Hisham Rashwan H, Braoudaki M, Youness RA. Circular RNAs: New layer of complexity evading breast cancer heterogeneity. Noncoding RNA Res 2023; 8:60-74. [PMID: 36380816 PMCID: PMC9637558 DOI: 10.1016/j.ncrna.2022.09.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/04/2022] [Accepted: 09/30/2022] [Indexed: 11/23/2022] Open
Abstract
Advances in high-throughput sequencing techniques and bioinformatic analysis have refuted the "junk" RNA hypothesis that was claimed against non-coding RNAs (ncRNAs). Circular RNAs (circRNAs); a class of single-stranded covalently closed loop RNA molecules have recently emerged as stable epigenetic regulators. Although the exact regulatory role of circRNAs is still to be clarified, it has been proven that circRNAs could exert their functions by interacting with other ncRNAs or proteins in their own physiologically authentic environment, regulating multiple cellular signaling pathways and other classes of ncRNAs. CircRNAs have also been reported to exhibit a tissue-specific expression and have been associated with the malignant transformation process of several hematological and solid malignancies. Along this line of reasoning, this review aims to highlight the importance of circRNAs in Breast Cancer (BC), which is ranked as the most prevalent malignancy among females. Notwithstanding the substantial efforts to develop a suitable anticancer therapeutic regimen against the heterogenous BC, inter- and intra-tumoral heterogeneity have resulted in an arduous challenge for drug development research, which in turn necessitates the investigation of other markers to be therapeutically targeted. Herein, the potential of circRNAs as possible diagnostic and prognostic biomarkers have been highlighted together with their possible application as novel therapeutic targets.
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Affiliation(s)
- Alyaa Dawoud
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
| | - Zeina Ihab Zakaria
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
| | - Hannah Hisham Rashwan
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
| | - Maria Braoudaki
- Clinical, Pharmaceutical, and Biological Science Department, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK
| | - Rana A. Youness
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
- Clinical, Pharmaceutical, and Biological Science Department, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK
- Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire hosted By Global Academic Foundation, New Administrative Capital, 11586, Cairo, Egypt
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18
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Zhu Y, Yan W, Xu S, Yu X, Sun S, Zhang S, Zhao R, Tao J, Li Y, Li C. Identification of an unrecognized circRNA associated with development of renal fibrosis. Front Genet 2023; 13:964840. [PMID: 36685959 PMCID: PMC9845265 DOI: 10.3389/fgene.2022.964840] [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: 06/09/2022] [Accepted: 12/01/2022] [Indexed: 01/05/2023] Open
Abstract
Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive. Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly. Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis. Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.
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Affiliation(s)
- Yun Zhu
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Weimin Yan
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Shuangyan Xu
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Xiaochao Yu
- Graduate School, Kunming Medical University, Kunming, China
| | - Shuo Sun
- Graduate School, Kunming Medical University, Kunming, China
| | | | - Ran Zhao
- Graduate School, Kunming Medical University, Kunming, China
| | - Jiayue Tao
- Graduate School, Kunming Medical University, Kunming, China
| | - Yunwei Li
- Department of Urology, The Third Hospital of Shandong Province, Jinan, China,*Correspondence: Yunwei Li, ; Cuie Li,
| | - Cuie Li
- Department of Geriatrics, The People’s Hospital of Yuxi City, Yuxi, China,*Correspondence: Yunwei Li, ; Cuie Li,
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19
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Liu Z, Zhang W, Tu C, Li W, Qi L, Zhang Z, Wan L, Yang Z, Ren X, Li Z. Prognostic and clinicopathologic significance of circZFR in multiple human cancers. World J Surg Oncol 2022; 20:268. [PMID: 36008845 PMCID: PMC9413939 DOI: 10.1186/s12957-022-02733-9] [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: 03/22/2022] [Accepted: 08/17/2022] [Indexed: 11/24/2022] Open
Abstract
Background Abnormally expressed in diverse cancers, circZFR has been correlated with clinical outcomes of cancer patients. Aim of this meta-analysis was to elucidate the prognostic role of circZFR in multiple human malignancies. Methods Literature retrieval was conducted by systematically searching on Pubmed, Web of Science, and the Cochrane Library up to December 2nd, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). The reliability of the pooled results was assessed through sensitivity analysis and the publication bias was measured by Begg’s and Egger’s test. Results A total of seventeen studies comprising 1098 Chinese patients were enrolled in this meta-analysis. Results demonstrated that high circZFR expression was correlated with an unfavorable OS (HR = 2.14, 95% CI 1.74, 2.64). High circZFR expression predicted larger tumor size (OR = 2.79, 95% CI 1.52, 5.12), advanced clinical stage (OR = 3.38, 95% CI 1.49, 7.65), tendentiousness of lymph node metastasis (LNM) (OR = 3.08, 95% CI 2.01, 4.71), and malignant grade (OR = 3.18, 95% CI 1.09, 9.30), but not related to age, gender, and distant metastasis (DM). Conclusions High circZFR expression was associated with unfavorable OS and clinicopathologic parameters including tumor size, clinical stage, LNM, and histology grade, implicating a promising prognostic factor in cancers. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02733-9.
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Affiliation(s)
- Zhongyue Liu
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Wenchao Zhang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Chao Tu
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Wenyi Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Lin Qi
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Zhiming Zhang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Lu Wan
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Zhimin Yang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Xiaolei Ren
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China. .,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
| | - Zhihong Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China. .,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
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20
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Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights. Int J Biol Macromol 2022; 220:973-984. [PMID: 35977596 DOI: 10.1016/j.ijbiomac.2022.08.085] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/19/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.
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21
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Tumor Cells-derived exosomal CircRNAs: Novel cancer drivers, molecular mechanisms, and clinical opportunities. Biochem Pharmacol 2022; 200:115038. [DOI: 10.1016/j.bcp.2022.115038] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/01/2022] [Accepted: 04/06/2022] [Indexed: 12/12/2022]
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22
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Cao F, Liu S, Li Z, Meng L, Sang M, Shan B. Activation of circ_0072088/miR-1261/PIK3CA pathway accelerates lung adenocarcinoma progression. Thorac Cancer 2022; 13:1548-1557. [PMID: 35474604 PMCID: PMC9161339 DOI: 10.1111/1759-7714.14369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of lung adenocarcinoma (LUAD). This study aimed to determine the role of circ_0072088 in LUAD. METHODS The existence and expression of circ_0072088 in human LUAD tissues and cell lines were determined through Sanger sequencing, quantitative reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization (FISH). Subsequently, the biological role of circ_0072088 was examined using loss-of-function assays in H1299 cells. Moreover, circ_0072088/miR-1261/PIK3CA pathway-mediated biological effects in H1299 were verified using bioinformatic prediction and experiments, including interaction analysis (FISH, luciferase reporter, and RNA-pulldown assays), and tumor biological function test (CCK8 and colony formation, wound healing, and transwell assays). Finally, miR-1261 and PIK3CA expression and LUAD patient survival were further analyzed using FISH, immunohistochemical staining, and the Kaplan-Meier plotter database, respectively. RESULTS First, an increase in circ_0072088 was confirmed in human LUAD tissues. Thereafter, it was mainly localized in the cytoplasm and was found to enhance cell proliferation, migration, and invasion of H1299 cells. Mechanistically, circ_0072088 directly downregulated miR-1261 expression, whereas increased PIK3CA gene expression was associated with poor overall survival of LUAD patients. The activation of the circ_0072088/miR-1261/PIK3CA regulatory pathway may play a significant role in the tumorigenesis and progression of LUAD. CONCLUSIONS Circ_0072088-dependent regulation of miR-1261/PIK3CA is important for cell proliferation, migration, and invasion during the tumorigenesis and progression of LUAD, warranting the need to consider the circ_0072088/miR-1261/PIK3CA regulatory pathway as a potential therapeutic target in patients with lung adenocarcinoma.
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Affiliation(s)
- Feng Cao
- Department of Radiation Oncologythe Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
| | - Sihua Liu
- Research Center, the Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
| | - Ziyi Li
- Research Center, the Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
| | - Lingjiao Meng
- Research Center, the Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
| | - Meixiang Sang
- Research Center, the Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
| | - Baoen Shan
- Research Center, the Fourth Hospital of HebeiMedical UniversityShijiazhuangChina
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23
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Ma L, Zhang M, Cao F, Han J, Han P, Wu Y, Deng R, Zhang G, An X, Zhang L, Song Y, Cao B. Effect of MiR-100-5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo. J Cell Mol Med 2022; 26:2543-2556. [PMID: 35411593 PMCID: PMC9077292 DOI: 10.1111/jcmm.17226] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
The growth of endometrial stromal cells (ESCs) at implantation sites may be a potential factor affecting the success rate of embryo implantation. Incremental proofs demonstrated that ncRNAs (e.g. miRNAs, lncRNAs and circRNAs) were involved in various biological procedures, including proliferation and apoptosis. In this study, the role of miR‐100‐5p on proliferation and apoptosis of goat ESCs in vitro and embryo implantation in vivo was determined. The mRNA expression of miR‐100‐5p was significantly inhibited in the receptive phase (RE) rather than in the pre‐receptive phase (PE). Overexpression of miR‐100‐5p suppressed ESCs proliferation and induced apoptosis. The molecular target of MiR‐100‐5p, HOXA1, was confirmed by 3′‐UTR assays. Meanwhile, the product of HOXA1 mRNA RT‐PCR increased in the RE more than that in the PE. The HOXA1‐siRNA exerted significant negative effects on growth arrest. Instead, incubation of ESCs with miR‐100‐5p inhibitor or overexpressed HOXA1 promoted the cell proliferation. In addition, Circ‐9110 which acted as a sponge for miR‐100‐5p reversed the relevant biological effects of miR‐100‐5p. The intrinsic apoptosis pathway was suppressed in ESCs, revealing a crosstalk between Circ‐9110/miR‐100‐5p/HOXA1 axis, PI3K/AKT/mTOR, and ERK1/2 pathways. To further evaluate the progress in study on embryo implantation regulating mechanism of miR‐100‐5p in vivo, the pinopodes of two phases were observed and analysed, suggesting that, as similar as in situ, miR‐100‐5p was involved in significantly regulating embryo implantation in vivo. Mechanistically, miR‐100‐5p performed its embryo implantation function through regulation of PI3K/AKT/mTOR and ERK1/2 pathways by targeting Circ‐9110/miR‐100‐5p/HOXA1 axis in vivo.
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Affiliation(s)
- Li Ma
- College of Animal Science and Technology, Northwest A&F University, Yangling, China.,Shaanxi University of Chinese Medicine, Xianyang, China
| | - Meng Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Fangjun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China.,Shaanxi Institute of Zoology, Xi'an, China
| | - Jincheng Han
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Peng Han
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Yeting Wu
- College of Food Science and Engineering, Northwest A&F University, Yangling, China
| | - Renyi Deng
- Department of Foreign Languages, Northwest A&F University, Yangling, China
| | - Guanghui Zhang
- College of Innovation and Experiment, Northwest A&F University, Yangling, China
| | - Xiaopeng An
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Lei Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Yuxuan Song
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Binyun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
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Ginckels P, Holvoet P. Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2022; 95:129-152. [PMID: 35370493 PMCID: PMC8961704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
High oxidative stress, Th1/Th17 immune response, M1 macrophage inflammation, and cell death are associated with cardiovascular diseases. Controlled oxidative stress, Th2/Treg anti-tumor immune response, M2 macrophage inflammation, and survival are associated with cancer. MiR-21 protects against cardiovascular diseases but may induce tumor growth by retaining the anti-inflammatory M2 macrophage and Treg phenotypes and inhibiting apoptosis. Down-regulation of let-7, miR-1, miR-9, miR-16, miR-20a, miR-22a, miR-23a, miR-24a, miR-26a, miR-29, miR-30a, miR-34a, miR-124, miR-128, miR-130a, miR-133, miR-140, miR-143-145, miR-150, miR-153, miR-181a, miR-378, and miR-383 may aid cancer cells to escape from stresses. Upregulation of miR-146 and miR-223 may reduce anti-tumor immune response together with miR-21 that also protects against apoptosis. MiR-155 and silencing of let-7e, miR-125, and miR-126 increase anti-tumor immune response. MiR expression depends on oxidative stress, cytokines, MYC, and TGF-β, and expression of silencing lncRNAs and circ-RNAs. However, one lncRNA or circ-RNA may have opposite effects by targeting several miRs. For example, PVT1 induces apoptosis by targeting miR-16a and miR-30a but inhibits apoptosis by silencing miR-17. In addition, levels of a non-coding RNA in a cell type depend not only on expression in that cell type but also on an exchange of microvesicles between cell types and tumors. Although we got more insight into the function of a growing number of individual non-coding RNAs, overall, we do not know enough how several of them interact in functional networks and how their expression changes at different stages of disease progression.
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Affiliation(s)
- Pieterjan Ginckels
- Department of Architecture, Brussels and Gent, KU Leuven, Leuven, Belgium
| | - Paul Holvoet
- Experimental Cardiology, KU Leuven, Leuven, Belgium,To whom all correspondence should be addressed: Paul Holvoet, Experimental
Cardiology, KU Leuven, Belgium; ; ORCID iD:
https://orcid.org/0000-0001-9201-0772
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25
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Tian X, Yang H, Fang Q, Quan H, Lu H, Wang X. Circ_ZFR affects FABP7 expression to regulate breast cancer progression by acting as a sponge for miR-223-3p. Thorac Cancer 2022; 13:1369-1380. [PMID: 35355424 PMCID: PMC9058297 DOI: 10.1111/1759-7714.14401] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Breast cancer (BC) is a common malignancy in women. Circular RNAs (circRNAs) have been reported to play a key role in the development of BC; however, the effect of circular RNA zinc finger RNA binding protein (circ_ZFR) in BC is unknown. METHODS Abundances of circ_ZFR, fatty acid binding protein 7 (FABP7), and microRNA-223-3p (miR-223-3p) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure of circ_ZFR was validated by RNase R treatment. Cell proliferation, migration, invasion, and apoptosis were assessed by colony formation, cell counting kit-8, Transwell, flow cytometry assays, respectively. All protein levels were determined by Western blot. Dual-luciferase reporter assay was used to confirm the relationship between miR-223-3p and circ_ZFR or FABP7. A xenograft model was established to understand the effect of circ_ZFR on BC cell growth in vivo. RESULTS The expression levels of circ_ZFR and FABP7 were higher in BC tissues and cell lines, whereas miR-223-3p expression was lower. Knockdown of circ_ZFR or FABP7 in BC cells reduced proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and induced apoptosis in vitro, whereas the opposite effects were observed in circ_ZFR-overexpressed cells. Furthermore, circ_ZFR might act as a sponge for miR-223-3p to regulate FABP7 expression, thereby promoting the progression of BC cells in vitro and in vivo. CONCLUSION Circ_ZFR might act as a miRNA sponge for miR-223-3p to regulate FABP7, thereby promoting proliferation, migration, invasion, and EMT of BC cells, and inhibiting cell apoptosis.
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Affiliation(s)
- Xiuling Tian
- Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Hong Yang
- Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Qian Fang
- Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Hongmei Quan
- Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Hongyu Lu
- Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Xin Wang
- Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
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26
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Zhou Y, Tang W, Zhuo H, Zhu D, Rong D, Sun J, Song J. Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/ nuclear factor -kappa B (NF-κB) pathway. Bioengineered 2022; 13:4786-4797. [PMID: 35139763 PMCID: PMC8973934 DOI: 10.1080/21655979.2022.2032972] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Chemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC.
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Affiliation(s)
- Yun Zhou
- Department of Ultrasonography, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Weiwei Tang
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Han Zhuo
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Deming Zhu
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dawei Rong
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jin Sun
- Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinhua Song
- Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; Nhc Key Laboratory of Living Donor Liver Transplantation, Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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27
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Liu L, Wang H, Yu S, Gao X, Liu G, Sun D, Jiang X. An Update on the Roles of circRNA-ZFR in Human Malignant Tumors. Front Cell Dev Biol 2022; 9:806181. [PMID: 35186956 PMCID: PMC8848330 DOI: 10.3389/fcell.2021.806181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/16/2021] [Indexed: 01/11/2023] Open
Abstract
CircRNAs (circular RNAs) are single-stranded RNAs that form covalently closed loops and function as important regulatory elements of the genome through multiple mechanisms. Increasing evidence had indicated that circRNAs, which might serve as either oncogenes or tumor suppressors, played vital roles in the pathophysiology of human diseases, especially in tumorigenesis and progression. CircRNA-ZFR (circular RNA zinc finger RNA binding protein) is a circular RNA that had attracted much attention in recent years. It has been found that circRNA-ZFR was abnormally expressed in a variety of malignant tumors, and its dysregulated expression was closely related to tumor stage, cancer metastasis and patients’ prognosis. Recent studies had shown that aberrantly expressed circRNA-ZFR could regulate the malignant biological behaviors of tumors through various mechanisms; further exploration of circRNA-ZFR expression in tumors and its regulation on malignant biological behaviors such as tumor proliferation, invasion and drug resistance will provide new ideas for clinical tumors diagnosis and treatment.
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28
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An C, Wang M, Yao W. Exhausting hsa_circ_0072088 restrains proliferation, motility and angiogenesis of breast carcinoma cells through regulating miR-1236-3p and RRM2 in a ceRNA pathway. Clin Breast Cancer 2022. [DOI: 10.1016/j.clbc.2022.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Xu J, Hao Y, Gao X, Wu Y, Ding Y, Wang B. CircSLC7A6 promotes the progression of Wilms' tumor via microRNA-107/ ABL proto-oncogene 2 axis. Bioengineered 2022; 13:308-318. [PMID: 34787058 PMCID: PMC8805947 DOI: 10.1080/21655979.2021.2001204] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/28/2021] [Indexed: 12/14/2022] Open
Abstract
The dysregulation of circular RNAs (circRNAs) has been proved to be involved in the carcinogenesis of various cancers. Nevertheless, the biological function of circSLC7A6 remains unclear in Wilms' tumor (WT). In our study, we found that circSLC7A6 was upregulated in cancerous WT tissues and cells. Cell apoptosis was increased while cell viability, migration, and invasion were repressed by circSLC7A6 silencing. Besides, circSLC7A6 knockdown suppressed WT tumor growth in vivo. miR-107 was identified as a direct target of circSLC7A6, and circSLC7A6 could negatively regulate miR-107 expression. In addition, circSLC7A6 knockdown inhibited WT progression, while the effect was partially abolished by the downregulation of miR-107. Additionally, ABL proto-oncogene 2 axis (ABL2) was verified as a downstream gene of miR-107, and circSLC7A6 could upregulate ABL2 expression by serving as a ceRNA of miR-107. Moreover, functional assays revealed that ABL2 overexpression reversed the impact of circSLC7A6 depletion on cell proliferation, migration, invasion, and apoptosis of WT. In conclusion, the present study demonstrated that circSLC7A6 facilitated WT progression by upregulating ABL2 through inhibiting miR-107 expression. These results suggested that circSLC7A6 might serve as a potential therapeutic target for WT.
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Affiliation(s)
- Jiaju Xu
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
| | - Ying Hao
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
| | - Xingjuan Gao
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
| | - Yanqiu Wu
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
| | - Yanjie Ding
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
| | - Baohong Wang
- Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai City, China
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circDENND4C Promotes Proliferation and Metastasis of Lung Cancer by Upregulating BRD4 Signaling Pathway. JOURNAL OF ONCOLOGY 2021; 2021:2469691. [PMID: 34876902 PMCID: PMC8645384 DOI: 10.1155/2021/2469691] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/01/2021] [Accepted: 11/05/2021] [Indexed: 11/17/2022]
Abstract
Objective To investigate the effects of circDENND4C on the malignant biological behavior of lung cancer and its downstream target genes and molecular mechanisms. Methods The expression of circDENND4C in lung cancer tissues and cells was detected. After transfection with silenced circDENND4C, the expression levels of circDENND4C, miR-141-3p, and BRD4 in lung cancer cells were detected by qRT-PCR. The targeting relationship between circDENND4C and miR-141-3p as well as miR-141-3p and BRD4 was verified. Cell activity was detected by CCK-8 and EdU assay. Transwell assay was used to detect the invasiveness of A549 and NCI-H1299 in each group. Effects of circDENND4C on proliferation and metastasis of lung cancer in nude mice were studied. Results In vitro and in vivo results showed that circDENND4C silencing reduced the proliferation, invasion, and metastasis of lung cancer cells. Mechanism studies showed that circDENND4C has a targeting relationship with miR-141-3p. However, miR-141-3p has a targeting relationship with BRD4. circDENND4C indirectly upregulated BRD4 through sponge adsorption of miR-141-3p, thereby promoting metastasis and proliferation of NSCLC. Conclusion circDENND4C, as an oncogene, promotes the proliferation, invasion, and metastasis of lung cancer cells.
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LncRNA4930473A02Rik promotes cardiac hypertrophy by regulating TCF7 via sponging miR-135a in mice. Cell Death Discov 2021; 7:378. [PMID: 34876564 PMCID: PMC8651675 DOI: 10.1038/s41420-021-00775-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/21/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Cardiac hypertrophy is a common pathological change accompanied by various cardiovascular diseases; however, its underlying mechanisms remain elusive. Mounting evidence indicates that long non-coding RNAs (lncRNAs) are novel transcripts involved in regulating multiple biological processes. However, little is known about their role in regulating cardiac hypertrophy. This study revealed a novel lncRNA4930473A02Rik (abbreviated as lncRNAA02Rik), which showed considerably increased expression in hypertrophic mouse hearts in vivo and angiotensin-II (Ang-II)-induced hypertrophic cardiomyocytes in vitro. Notably, lncRNAA02Rik knockdown partly ameliorated Ang-II induced hypertrophic cardiomyocytes in vitro and hypertrophic mouse heart function in vivo, whereas lncRNAA02Rik overexpression promoted cardiac hypertrophy in vitro. Furthermore, lncRNAA02Rik acted as a competing endogenous RNA by sponging miR-135a, while forced expression of lncRNAA02Rik could repress its activity and expression. Furthermore, forcing miR-135a overexpression exerted a significant protective effect against cardiac hypertrophy by inhibiting the activity of its downstream target TCF7, a critical member of Wnt signaling, and the protective effect could be reversed by AMO-135a. Luciferase assay showed direct interactions among lncRNAA02Rik, miR-135a, and TCF7. Altogether, our study demonstrated that lncRNAA02Rik upregulation could promote cardiac hypertrophy development via modulating miR-135a expression levels and TCF7 activity. Therefore, lncRNAA02Rik inhibition might be considered as a novel potential therapeutic strategy for cardiac hypertrophy.
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Xu R, Yin S, Zheng M, Pei X, Ji X. Circular RNA circZFR Promotes Hepatocellular Carcinoma Progression by Regulating miR-375/HMGA2 Axis. Dig Dis Sci 2021; 66:4361-4373. [PMID: 33433801 DOI: 10.1007/s10620-020-06805-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 12/17/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Mounting evidence indicates that circular RNAs (circRNAs) have vital roles in human diseases, especially in cancers. AIMS The aim of this study was to explore the biological functions and underlying mechanism of circRNA zinc finger RNA binding (circZFR) in hepatocellular carcinoma (HCC). METHODS The expression levels of circZFR, microRNA-375 (miR-375) and high mobility group A2 (HMGA2) were detected by qRT-PCR or western blot assay. Glycolytic metabolism was examined via the measurement of extracellular acidification rate, oxygen consumption rate, glucose uptake, lactate production, and ATP level. MTT assay and flow cytometry were used to assess cell proliferation and cell apoptosis, respectively. The interaction between miR-375 and circZFR or HMGA2 was verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The mice xenograft model was established to investigate the role of circZFR in vivo. RESULTS CircZFR and HMGA2 were upregulated while miR-375 was downregulated in HCC tissues and cells. CircZFR silence inhibited HCC progression by inhibiting cell proliferation, glycolysis and tumor growth and promoting apoptosis. MiR-375 was a direct target of circZFR and its knockdown reversed the inhibitory effect of circZFR silence on the progression of HCC cells. Moreover, HMGA2 was a downstream target of miR-375, and miR-375 suppressed proliferation and glycolysis and induced apoptosis by targeting HMGA2 in HCC cells. Besides, circZFR acted as a molecular sponge of miR-375 to regulate HMGA2 expression. CONCLUSION Knockdown of circZFR suppressed the progression of HCC by upregulating miR-375 and downregulating HMGA2, providing new insight into the pathogenesis of HCC.
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Affiliation(s)
- Rui Xu
- Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 1 Swan Lake Road, New District of Political Affairs and Culture, Hefei, 230036, Anhui, China
| | - Shiwu Yin
- Department of Interventional Radiology, The Second People's Hospital of Hefei, Hefei, 230000, Anhui, China
| | - Meng Zheng
- Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 1 Swan Lake Road, New District of Political Affairs and Culture, Hefei, 230036, Anhui, China
| | - Xiaohong Pei
- Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 1 Swan Lake Road, New District of Political Affairs and Culture, Hefei, 230036, Anhui, China
| | - Xuebing Ji
- Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 1 Swan Lake Road, New District of Political Affairs and Culture, Hefei, 230036, Anhui, China.
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Chen D, Ping S, Xu Y, Wang M, Jiang X, Xiong L, Zhang L, Yu H, Xiong Z. Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications. Front Cell Dev Biol 2021; 9:732036. [PMID: 34805143 PMCID: PMC8595133 DOI: 10.3389/fcell.2021.732036] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 10/18/2021] [Indexed: 01/19/2023] Open
Abstract
Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.
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Affiliation(s)
- Di Chen
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuai Ping
- Department of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yushuang Xu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengmeng Wang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Jiang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lina Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Zhang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Honglu Yu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhifan Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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TÜNCEL Ö, KARA M, YAYLAK B, ERDOĞAN İ, AKGÜL B. Noncoding RNAs in apoptosis: identification and function. Turk J Biol 2021; 46:1-40. [PMID: 37533667 PMCID: PMC10393110 DOI: 10.3906/biy-2109-35] [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: 09/11/2021] [Revised: 02/08/2022] [Accepted: 11/14/2021] [Indexed: 08/04/2023] Open
Abstract
Apoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein-coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.
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Affiliation(s)
- Özge TÜNCEL
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Merve KARA
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Bilge YAYLAK
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - İpek ERDOĞAN
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
| | - Bünyamin AKGÜL
- Non-coding RNA Laboratory, Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir,
Turkey
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Han J, Yang Z, Zhao S, Zheng L, Tian Y, Lv Y. Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression. Eur J Clin Invest 2021; 51:e13592. [PMID: 34032284 DOI: 10.1111/eci.13592] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. METHODS The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. RESULTS Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. CONCLUSION Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.
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Affiliation(s)
- Jinzhu Han
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zixin Yang
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shan Zhao
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Likang Zheng
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanhua Tian
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingqian Lv
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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36
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Xiong H, Yu H, Jia G, Yu J, Su Y, Zhang J, Zhou J. circZFR regulates thyroid cancer progression by the miR-16/MAPK1 axis. ENVIRONMENTAL TOXICOLOGY 2021; 36:2236-2244. [PMID: 34323000 DOI: 10.1002/tox.23337] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 07/12/2021] [Accepted: 07/17/2021] [Indexed: 06/13/2023]
Abstract
Previous studies have identified the dysregulation of various circRNAs in many types of human cancers including thyroid cancer (TC). Circular RNA ZFR (circZFR) serves as an oncogenic circRNA in TC. However, the detailed molecular mechanism of circZFR in TC progression remains to be further explored. CircZFR and miR-16 expressions in TC cells were analyzed through qRT-PCR. Cell viability, invasion, and apoptosis were detected using CCK-8, transwell invasion assay, and flow cytometry analysis, respectively. The relationship between circZFR and miR-16 was explored using luciferase reporter assay, RNA pull-down assay, and qRT-PCR. The relationship between miR-16 and mitogen-activated protein kinase 1 (MAPK1) was explored using luciferase reporter assay and western blot analysis. Results showed that circZFR was upregulated and miR-16 was downregulated in TC cells. CircZFR knockdown inhibited the viability and invasion and induced apoptosis in TC cells. CircZFR inhibited miR-16 expression by sponging miR-16 and miR-16 repressed MAPK1 expression by targeting MAPK1. Moreover, circZFR positively regulated MAPK1 expression in TC cells by serving as a ceRNA of miR-16. Mechanistically, circZFR knockdown-induced inhibition of cell viability and invasion and promotion of apoptosis were overturned after miR-16 downregulation and promotion of MAPK1. Collectively, circZFR knockdown retarded TC progression by sponging miR-16 and modulating MAPK1 expression.
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Affiliation(s)
- Hui Xiong
- Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, China
- Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital, Nanyang, China
| | - Huimei Yu
- Department of Endocrinology, Huaiyin Hospital, Huai'an, China
| | - Guangwei Jia
- Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, China
| | - Jinsong Yu
- Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital, Nanyang, China
- Department of General Surgery, Nanyang First People's Hospital, Nanyang, China
| | - Yang Su
- Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, China
| | - Jianliang Zhang
- Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, China
| | - Jin Zhou
- Department of Ultrasound Imaging, The Affiliated Huai'an Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huai'an, China
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Ghafouri-Fard S, Honarmand Tamizkar K, Jamali E, Taheri M, Ayatollahi SA. Contribution of circRNAs in gastric cancer. Pathol Res Pract 2021; 227:153640. [PMID: 34624593 DOI: 10.1016/j.prp.2021.153640] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 12/13/2022]
Abstract
Gastric cancer (GC) is one of the most commonly diagnosed neoplasms in the world. A number of environmental and lifestyle factors, particularly chronic infection with Helicobacter pylori, have been found to partake in the pathogenesis of GC. The advent of high-throughput genome and transcriptome analysis has enhanced the knowledge about molecular mechanisms of the pathogenesis of GC. However, data regarding the expression of several circRNAs, such as circLMTK2, are not consistent. We explain the role of circRNAs in the development of GC. We searched databases for the newest publications using the terms gastric cancer and circRNA. Each circRNA alteration, downstream targets, its impacts on cancer cells, and the prognostic and diagnostic roles of these circRNAs have been discussed. Taken together, circRNAs can be putative biomarkers in GC and potential targets for the treatment of this cancer. Yet, this field is still in its infancy and needs further experiments for reaching the clinical application. As these transcripts are stable in circulation, they can be used in non-invasive methods of cancer detection and patients' follow-up.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kasra Honarmand Tamizkar
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elena Jamali
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Liu Z, Li M. Circular RNAs and their role in renal cell carcinoma: a current perspective. Cancer Cell Int 2021; 21:469. [PMID: 34488780 PMCID: PMC8422676 DOI: 10.1186/s12935-021-02181-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 08/27/2021] [Indexed: 02/07/2023] Open
Abstract
Circular RNAs (circRNAs) are a new class of long non-coding RNAs, that results from a special type of alternative splicing referred to as back-splicing. They are widely distributed in eukaryotic cells and demonstrate tissue-specific expression patterns in humans. CircRNAs actively participate in various important biological activities like gene transcription, pre-mRNA splicing, translation, sponging miRNA and proteins, etc. With such diverse biological functions, circRNAs not only play a crucial role in normal human physiology, as well as in multiple diseases, including cancer. In this review, we summarized our current understanding of circRNAs and their role in renal cell carcinoma (RCC), the most common cancer of kidneys. Studies have shown that the expression level of several circRNAs are considerably varied in RCC samples and RCC cell lines suggesting the potential role of these circRNAs in RCC progression. Several circRNAs promote RCC development and progression mostly via the miRNA/target gene axis making them ideal candidates for novel anti-cancer therapy. Apart from these, there are a few circRNAs that are significantly downregulated in RCC and overexpression of these circRNAs leads to suppression of RCC growth. Differential expression patterns and novel functions of circRNAs in RCC suggest that circRNAs can be utilized as potential biomarkers and therapeutic targets for RCC therapy. However, our current understanding of the role of circRNA in RCC is still in its infancy and much comprehensive research is needed to achieve clinical translation of circRNAs as biomarkers and therapeutic targets in developing effective treatment options for RCC.
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Affiliation(s)
- Zhongyuan Liu
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China
| | - Ming Li
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China.
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Peng Y, Hu S, Zhang K, Wang Y, Rouzi M, Zhou D, Yang R. Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway. Cancer Manag Res 2021; 13:4829-4840. [PMID: 34168502 PMCID: PMC8216666 DOI: 10.2147/cmar.s287575] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 03/18/2021] [Indexed: 02/05/2023] Open
Abstract
Introduction Oral squamous cell carcinoma (OSCC) means oral epithelial cell injury caused by multiple genetic mutations of the cells. Dysregulation of microRNAs (miRs) can disrupt the progression of OSCC. This study explored the mechanism of miR-130a in OSCC progression. Methods miR-130a expression in OSCC cell lines was analyzed. Functional assays were utilized to test the alterations of OSCC cell proliferation, apoptosis and epithelial–mesenchymal transition (EMT) with downregulated miR-130a, shRNA-PTEN or/and YAP inhibitor verteporfin. Then, dual-luciferase reporter gene assay was performed to clarify the targeting relation between miR-130a and PTEN. After that, Hippo-YAP pathway-related protein levels were tested. Moreover, xenograft transplantation was applied to confirm the in vitro experiments. Results Highly expressed miR-130a was observed in OSCC cell lines. Silenced miR-130a reduced OSCC proliferation, metastasis, invasion and EMT while propelled apoptosis. Furthermore, miR-130a targeted PTEN to promote the OSCC progression. Downregulation of PTEN reversed the inhibition of silencing miR-130a on proliferation and migration of SCC-4 cells. miR-130a targeted PTEN to inactivate the Hippo-YAP axis. OSCC progression was notably promoted by a combination of YAP inhibitor verteporfin and miR-130a inhibitor. Additionally, silenced miR-130a inhibited OSCC progression in vivo. Discussion Silencing miR-130a inhibited OSCC progression by targeting PTEN and activating the Hippo-YAP axis. This investigation may provide novel insight for OSCC treatment.
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Affiliation(s)
- Yiran Peng
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China.,Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Shoushan Hu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China
| | - Kun Zhang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China
| | - Yuru Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China
| | - Maierdanjiang Rouzi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China
| | - Dan Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China
| | - Ran Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, 610041, People's Republic of China.,Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
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40
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Zhang L, Tao H, Li J, Zhang E, Liang H, Zhang B. Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma. Aging (Albany NY) 2021; 13:15990-16008. [PMID: 34049287 PMCID: PMC8266324 DOI: 10.18632/aging.203056] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 04/09/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The competing endogenous RNAs (ceRNAs) hypothesis has received increasing attention as a novel explanation for tumorigenesis and cancer progression. However, there is still a lack of comprehensive analysis of the circular RNA (circRNA)-long non-coding RNA (lncRNA)-miRNA-mRNA ceRNA network in hepatocellular carcinoma (HCC). METHODS RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were employed to identify Differentially Expressed mRNAs (DEmRNAs), DElncRNAs, and DEcircRNAs between HCC and normal tissues. Candidates were identified to construct networks through a comprehensive bioinformatics strategy. A prognostic mRNA signature was established based on data from TCGA database and validated using data from the GEO database. Then, the HCC prognostic circRNA-lncRNA-miRNA-mRNA ceRNA network was established. Finally, the expression and function of an unexplored hub gene, deoxythymidylate kinase (DTYMK), was explored through data mining. The results were examined using clinical samples and in vitro experiments. RESULTS We constructed a prognostic signature with seven target mRNAs by univariate, lasso and multivariate Cox regression analyses, which yielded 1, 3 and 5-year AUC values of 0.797, 0.733 and 0.721, respectively, indicating its sensitivity and specificity in the prognosis of HCC. Moreover, the prognostic signature could be validated in GSE14520. The prognostic ceRNA network of 21 circRNAs, 15 lncRNAs, 5 miRNAs, and 7 mRNAs was established according to the targeting relationship between 7 hub mRNAs and other RNAs. Our experiment results indicated that the depletion of DTYMK inhibited liver cancer cell proliferation and invasion. CONCLUSIONS The network revealed in this study may help comprehensively elucidate the ceRNA mechanisms driving HCC, and provide novel candidate biomarkers for evaluating the prognosis of HCC.
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Affiliation(s)
- Lu Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
| | - Haisu Tao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
| | - Jiang Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
| | - Erlei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
| | - Huifang Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.,Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan 430030, Hubei, China
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Warburg effect-promoted exosomal circ_0072083 releasing up-regulates NANGO expression through multiple pathways and enhances temozolomide resistance in glioma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:164. [PMID: 33975615 PMCID: PMC8111743 DOI: 10.1186/s13046-021-01942-6] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 04/11/2021] [Indexed: 12/20/2022]
Abstract
Background Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3’UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. Methods TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. Results circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. Conclusion Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-01942-6.
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Liu B, Yan L, Chi Y, Sun Y, Yang X. Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis. J Ovarian Res 2021; 14:60. [PMID: 33926489 PMCID: PMC8086133 DOI: 10.1186/s13048-021-00808-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 04/13/2021] [Indexed: 01/01/2023] Open
Abstract
Background Abnormally expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC). Methods The relative expression levels of lncRNA AFAP1-AS1, microRNA (miR)-107 and pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA were assessed by quantitative real-time PCR. PDK4, PCNA and cyclin D1 expression levels were determined using Western blot analysis. Bioinformatics analysis and dual-luciferase gene reporter assay were conducted for identifying and validating the binding sequences between AFAP1-AS1 and miR-107, as well as between miR-107 and PDK4. Cell counting kit-8 assay was employed for detecting cell proliferation. Cell migration and invasion abilities were examined using Transwell assays. Results The present study revealed that AFAP1-AS1 expression was elevated in OC cells and tissues. AFAP1-AS1 expression and FIGO stage were positively correlated. AFAP1-AS1 knockdown repressed OC cell proliferation, migration and invasion. AFAP1-AS1 functioned as a sponge of miR-107, and miR-107 reversed the effects of AFAP1-AS1 on OC cells. It was validated that miR-107 was able to bind to PDK4, and AFAP1-AS1 regulated PDK4 expression by competitively binding with miR-107. Additionally, miR-107 modulated OC cell proliferation, migration and invasion via targeting PDK4. Conclusions LncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/PDK4 axis.
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Affiliation(s)
- Bao Liu
- Chongqing Health Center for Women and Children, Chongqing, 401147, China
| | - Li Yan
- Chongqing Health Center for Women and Children, Chongqing, 401147, China.
| | - Yugang Chi
- Chongqing Health Center for Women and Children, Chongqing, 401147, China
| | - Yuhan Sun
- Chongqing Health Center for Women and Children, Chongqing, 401147, China
| | - Xiaoyu Yang
- Chongqing Health Center for Women and Children, Chongqing, 401147, China
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Liu J, Han Y, Hu S, Cai Y, Yang J, Ren S, Zhao Y, Lu T, Zhou X, Wang X. Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η. Front Cell Dev Biol 2021; 9:667800. [PMID: 33987186 PMCID: PMC8111223 DOI: 10.3389/fcell.2021.667800] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 03/18/2021] [Indexed: 12/28/2022] Open
Abstract
Exosomes, nanometer-sized membranous vesicles in body fluids, have emerged as promising non-invasive biomarkers for cancer diagnosis. However, the function of exosomes in diffuse large B-cell lymphoma (DLBCL) remains elusive. This study aimed to investigate the role of exosomal miR-107 in lymphomagenesis and explore its clinical significance. In this study, decreased exosomal miR-107, miR-375-3p, and upregulated exosomal miR-485-3p were detected in the plasma of DLBCL patients and showed potential diagnostic value. Downregulated miR-107 expression was associated with advanced Ann Arbor stage, high IPI score, LDH, and β2-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion in vitro, and repressed tumor growth in vivo. Moreover, the downregulation of miR-107 went in the opposite direction. The target genes of miR-107 were mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways. Notably, upregulated 14-3-3η (YWHAH) was suppressed by miR-107 in DLBCL, suggesting that miR-107 may restrain tumorigenesis by targeting 14-3-3η. In summary, this study unveils the function of miR-107 in lymphomagenesis, highlighting its potential as a diagnostic and prognostic indicator and as a new therapeutic target in the management of DLBCL.
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Affiliation(s)
- Jiarui Liu
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yang Han
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shunfeng Hu
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yiqing Cai
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Juan Yang
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shuai Ren
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yi Zhao
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tiange Lu
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiangxiang Zhou
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.,School of Medicine, Shandong University, Jinan, China.,Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.,Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.,National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xin Wang
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.,School of Medicine, Shandong University, Jinan, China.,Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.,Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.,National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
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Hatibaruah A, Rahman M, Agarwala S, Singh SA, Gupta S, Paul P. Circular RNAs in cancer and diabetes. J Genet 2021. [DOI: 10.1007/s12041-021-01268-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Luo L, Miao P, Ming Y, Tao J, Shen H. Circ-ZFR Promotes Progression of Bladder Cancer by Upregulating WNT5A Via Sponging miR-545 and miR-1270. Front Oncol 2021; 10:596623. [PMID: 33928018 PMCID: PMC8076638 DOI: 10.3389/fonc.2020.596623] [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: 08/19/2020] [Accepted: 12/16/2020] [Indexed: 12/20/2022] Open
Abstract
Background Bladder cancer is one of the most common cancers all over the world. CircZFR is a circular RNA and has been implicated in tumor generation and invasion. However, the exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further to probe into the association between circ-ZFR, miR-545/miR-1270 and WNT5A. Methods The expression of circZFR in BCa was quantified by qRT-PCR and was positively correlated with the prognosis of BCa patients. Next, the stable knockdown of circZFR BCa cell lines was established and the resulting capacities of proliferation, migration and invasion were measured. The association of circZFR with miR-1270/miR-545 was predicted by circinteractome prediction, and was confirmed by luciferase assay as well as RNA pull down assay. Furthermore, miRNA inhibitors, WNT5A overexpression and Pearson correlation analysis were used to examine the relationship between circZFR, miR-1270/miR-545 and WNT5A. Results The expression of CircZFR was up-regulated both in BCa tissues and in BCa cell lines, and was positively correlated with patient survival rates. Blocking of circZFR's expression by RNA inhibitors suppressed the proliferation, migration and invasion of BCa cells both in vitro and in vivo. On the other hand, overexpression of target miRNA supported that circZFR directly interact with miR-545 and miR-1270. Moreover, we demonstrated that circZFR promotes the progression of BCa by upregulating WNT5A's expression via sponging miR-545 and miR-1270. Conclusions CircZFR promotes the proliferation, migration and invasion of BCa cells by upregulating WNT5A signaling pathway via sponging miR-545 and miR-1270. These results provide new insights into the molecular mechanism of circZFR in BCa progression, and more important, a novel target for BCa clinical treatment.
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Affiliation(s)
- Liping Luo
- Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Pingping Miao
- Department of Nephrology, The Traditional Chinese Medicine Hospital of Luzhou City, Luzhou, China
| | - Yao Ming
- Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Jie Tao
- Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Hongchun Shen
- Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.,College of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China
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Gong J, Du C, Sun N, Xiao X, Wu H. Circular RNA hsa_circ_0005397 promotes hepatocellular carcinoma progression by regulating the miR-326/PDK2 axis. J Gene Med 2021; 23:e3332. [PMID: 33783904 DOI: 10.1002/jgm.3332] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 03/17/2021] [Accepted: 03/24/2021] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Circular RNAs (circRNAs) are associated with the initiation and progression of cancer. However, the biological functions and underlying mechanism of hsa_circ_0005397 in hepatocellular carcinoma (HCC) have not been fully elucidated. METHODS Hemotoxylin and eosin staining was used to assess histological changes. The expression levels of hsa_circ_0005397, miR-326 and pyruvate dehydrogenase kinase 2 (PDK2) were measured by a quantitative real-time polymerase chain reaction. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell cycle distribution and apoptosis were detected by flow cytometry analysis. Caspase-3 activity was determined by a caspase-3 activity kit. Wound healing and transwell assays were used to evaluate cell migration and invasion. A western blot assay was performed to measure the expression of cyclin D1, p21, matrix metalloproteinase (MMP)2, MMP9, PDK2 and PCNA. The interaction between miR-326 and hsa_circ_0005397 or PDK2 was confirmed by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft tumor models were established to confirm the role of hsa_circ_0005397 in vivo. RESULTS Hsa_circ_0005397 and PDK2 were up-regulated, whereas miR-326 was down-regulated in HCC tissues and cells. Hsa_circ_0005397 knockdown inhibited cell proliferation and metastasis, and promoted apoptosis. miR-326 was a direct target of hsa_circ_0005397, and inhibition of miR-326 reversed the inhibitory effect of hsa_circ_0005397 silencing on HCC progression. Moreover, PDK2 was a direct target of miR-326 and PDK2 overexpression abated the anti-cancer roles of miR-326 in HCC. Additionally, hsa_circ_0005397 regulated PDK2 expression by sponging miR-326. Furthermore, hsa_circ_0005397 down-regulation suppressed tumor growth by up-regulating miR-326 and down-regulating PDK2. CONCLUSIONS Hsa_circ_0005397 facilitates HCC progression by regulating the miR-326/PDK2 axis, providing a promising circRNA-targeted therapy for HCC.
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Affiliation(s)
- Jianzhuang Gong
- Department of Digestive Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Chenxu Du
- Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Nai Sun
- Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Xingguo Xiao
- Department of Digestive Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Huili Wu
- Department of Digestive Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
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Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A. Biosci Rep 2021; 40:226003. [PMID: 32766708 PMCID: PMC7426631 DOI: 10.1042/bsr20201313] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 08/05/2020] [Accepted: 08/06/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. METHODS The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. RESULTS Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. CONCLUSION Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.
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Guo T, Wang W, Ji Y, Zhang M, Xu G, Lin S. LncRNA PROX1-AS1 Facilitates Gastric Cancer Progression via miR-877-5p/PD-L1 Axis. Cancer Manag Res 2021; 13:2669-2680. [PMID: 33776485 PMCID: PMC7989960 DOI: 10.2147/cmar.s275352] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/26/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction Growing evidences imply that multiple long non-coding RNAs (lncRNAs) play a significant role in the treatment of cancer. Therefore, it is of great significance to discover new biomarkers or therapeutic targets of gastric cancer (GC). However, the potential molecular mechanism of lncPROX1-AS1 in GC remains unknown. The objective of current study is to investigate the effect of PROX1-AS1 in GC. Methods Thus, we detect that PROX1-AS1 is over-expressed in tissues and cell lines of GC using qRT-PCR analysis. CCK-8, colony formation, flow cytometry, wounding healing and transwell analyses were performed to explore the effect of PROX1-AS1 on GC malignant behaviors. Results It is further disclosed that silencing of PROX1-AS1 represses cell proliferation, migration, and invasion, whereas promotes cell apoptosis in GC. Bioinformatics analysis suggests that miR-877-5p is negatively regulated by PROX1-AS1 and ectopic of miR-877-5p alleviates the malignant behaviors of GC. Subsequently, miR-877-5p suppresses the activity of PD-L1-3ʹ UTR. At last, rescue assays demonstrated that the GC progression is suppressed by sh-PROX1-AS1 and facilitated on account of miR-877-5p inhibitors and then is retrieved by sh-PD-L1. Discussion Our findings reveal that PROX1-AS1 exerts its role via miR-877-5p/PD-L1 axis in the GC progression, suggesting that PROX1-AS1 may represent a new therapeutic target for the diagnosis and treatment of GC patients.
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Affiliation(s)
- TianWei Guo
- Department of Pathology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, People's Republic of China
| | - Wei Wang
- Department of Pathology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, People's Republic of China
| | - YueXia Ji
- Department of Pathology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, People's Republic of China
| | - Min Zhang
- Department of Pathology, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, People's Republic of China
| | - GuoYing Xu
- School of Medical Technology, Jiangsu College of Nursing, Huai'an, Jiangsu, People's Republic of China
| | - Sen Lin
- The Affiliated Huai'an Hospital of Xuzhou Medical University and the Second People's Hospital of Huai'an, Huai'an, Jiangsu, People's Republic of China
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Shen M, Zhang W, Wang B. The Effect of LncRNA Zinc Finger E-Box-Binding Homeobox 1 Antisense 1 on the Biological Characteristics of Gastric Cancer Cells by Regulating the MiR-200b/Wnt1 Axis. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In recent decades, most gastric cancer patients are diagnosed in the advanced disease stage with poor prognosis, and more than half of the advanced-stage patients will relapse. This research explores lncRNA ZEB1-AS1’s effect on gastric cancer cell proliferation, invasion, apoptosis
via regulating the miR-200b/Wnt1 molecular axis. ZEB1-AS1 and miR-200b expressions in BGC-803, SGC-7901, MKN-45, and AGS cells were measured by qRT-PCR. ZEB1-AS1 siRNA, miR-200b mimics, and miR-200b mimics + pcDNA3.1-ZEB1-AS1 were transfected into BGC-803 cells to study their respective effect
on cell proliferation, invasion, apoptosis using CCK-8 and Transwell assays and flow cytometry, respectively. Dual-luciferase reporter gene assay is used to detect the luciferase activity of ZEB1-AS1 WT or MUT and Wnt1 WT or MUT after co-transfecting with miR-200b mimics. The expression of
miR-200b in BGC-803 cells with knocked down or overexpressed ZEB1-AS1 was quantified with qRT-PCR. Western blot analysis was used to detect the protein level of Wnt1 in BGC-803 cells with upregulated or downregulated miR-200b expression. Data showed that ZEB1-AS1 expression was significantly
raised when miR-200b expression was reduced (P < 0.05). BGC-803 cells were selected for follow-up experiments. ZEB1-AS1, Wnt1, and miR-200b were found to have a targeted regulatory relationship. The knockdown of ZEB1-AS1 and upregulation of miR-200b can hinder BGC-803 cell proliferation
and invasion and expedite apoptosis. ZEB1-AS1 and miR-200b overexpression can reverse the effect of miR-200b upregulation on BGC-803 cell proliferation, invasion, and apoptosis. Therefore, lncRNA ZEB1-AS1 could impede gastric cancer cell proliferation and invasion and accelerate apoptosis
via the regulation of the miR-200b/Wnt1 molecular axis.
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Affiliation(s)
- Minghai Shen
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou 310023, Zhejiang, PR China
| | - Weidong Zhang
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou 310023, Zhejiang, PR China
| | - Bei Wang
- Department of Division of Hepatobiliary and Pancreatic Surgery, First Affifiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, PR China
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Zhang L, Wu R, Xu MJ, Sha J, Xu GY, Wu J, Zhang PA. MiRNA-107 contributes to inflammatory pain by down-regulating GLT-1 expression in rat spinal dorsal horn. Eur J Pain 2021; 25:1254-1263. [PMID: 33559250 DOI: 10.1002/ejp.1745] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Inflammatory pain is a severe clinical problem that affects the quality of life in patients. However, the currently available treatments for inflammatory pain have limited effect and even causes severe side effects. The aim of this study was to investigate the roles of miRNA-107 and glutamate transporter 1 (GLT-1) in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). METHODS Paw withdrawal threshold (PWT) of rats was measured by von Frey Filaments. The expressions of miRNA-107 and GLT-1 in the lumbar spinal dorsal horn (L4-L6) were measured with real-time quantitative PCR and western blotting analysis. Fluorescent in situ hybridization and fluorescent-immunohistochemistry were employed to detect the expression of miRNA-107, GLT-1 and co-location of miRNA-107 with GLT-1. RESULTS Injection of CFA significantly reduced PWT of rats. The miRNA-107 expression level was obviously up-regulated while the GLT-1 expression level was decreased in the spinal dorsal horn of CFA rats. miRNA-107 and GLT-1 were co-expressed in the same cells of the spinal dorsal horn in CFA rats. Ceftriaxone, a selective activator of GLT-1, obviously increased the PWT of CFA rats. Furthermore, antagomir of miRNA-107 reversed the down-regulation of GLT-1 and alleviated CFA-induced mechanical allodynia of CFA rats. CONCLUSIONS These results suggest that an increase of miR-107 contributes to inflammatory pain through downregulating GLT-1 expression, implying a promising strategy for pain therapy. SIGNIFICANCE The currently available treatments for inflammatory pain has limited effect even causes severe side effects. MiRNAs may have important diagnostic and therapeutic potential in inflammatory pain. In present study, we show a potential spinal mechanism of allodynia in rat inflammatory pain model induced by CFA. Increased miR-107 contribute to inflammatory pain by targeting and downregulating GLT-1 expression, implying a promising strategy for inflammatory pain.
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Affiliation(s)
- Ling Zhang
- Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China
| | - Rui Wu
- Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Mei-Jie Xu
- Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China
| | - Jie Sha
- JingJiang People's Hospital, Jingjiang, China
| | - Guang-Yin Xu
- Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Jian Wu
- JingJiang People's Hospital, Jingjiang, China
| | - Ping-An Zhang
- Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
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