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Hamdy NM, Zaki MB, Abdelmaksoud NM, Ismail RA, Abd-Elmawla MA, Rizk NI, Fathi D, Abulsoud AI. Insights into the genetic and epigenetic mechanisms governing X-chromosome-linked-miRNAs expression in cancer; a step-toward ncRNA precision. Int J Biol Macromol 2025; 289:138773. [PMID: 39675615 DOI: 10.1016/j.ijbiomac.2024.138773] [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: 12/04/2024] [Revised: 12/09/2024] [Accepted: 12/11/2024] [Indexed: 12/17/2024]
Abstract
Sex chromosomes play a significant role in establishing sex-specific differences in gene expression, thereby contributing to phenotypic diversity and susceptibility to various diseases. MicroRNAs (miRNAs), which are small non-coding RNAs encoded by both the X and Y chromosomes, exhibit sex-specific regulatory characteristics. Computational analysis has identified several X-linked miRNAs differentially expressed in sex-specific cancers. This review aims to elucidate the genetic and epigenetic mechanisms that govern the sex-specific expression of X- and Y-linked miRNAs, with particular attention to their functional role in regulating diverse cellular processes in different cancer pathways. In addition, this review provides a comprehensive understanding of the targeted therapeutic interventions and critical insights into the potential clinical implications of targeting sex-specific miRNAs. In conclusion, this review opens new horizons for further research to effectively translate these findings into viable treatment options.
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Affiliation(s)
- Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | | | - Rehab A Ismail
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Kasr Al-Ainy, Cairo 11562, Egypt
| | - Nehal I Rizk
- Department of Biochemistry, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo 11786, Egypt
| | - Doaa Fathi
- Department of Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21526, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al Azhar University, Nasr City, Cairo 11231, Egypt
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2
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Jame-Chenarboo F, Reyes JN, Twells NM, Ng HH, Macdonald D, Hernando E, Mahal LK. Screening the human miRNA interactome reveals coordinated up-regulation in melanoma, adding bidirectional regulation to miRNA networks. SCIENCE ADVANCES 2025; 11:eadr0277. [PMID: 39792681 PMCID: PMC11721578 DOI: 10.1126/sciadv.adr0277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 12/06/2024] [Indexed: 01/12/2025]
Abstract
Cellular protein expression is coordinated posttranscriptionally by an intricate regulatory network. The current presumption is that microRNAs (miRNAs) work by repression of functionally related targets within a system. In recent work, up-regulation of protein expression via direct interactions of messenger RNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation. Herein, we demonstrate coordinated up-regulation of functionally coupled proteins by miRNA. We focused on CD98hc, the heavy chain of the amino acid transporter LAT-1, and α-2,3-sialyltransferases ST3GAL1 and ST3GAL2, which are critical for CD98hc stability in melanoma. Profiling miRNA regulation using our high-throughput miRFluR assay, we identified miRNA that up-regulated the expression of both CD98hc and either ST3GAL1 or ST3GAL2. These co-up-regulating miRNAs were enriched in melanoma datasets associated with transformation and progression. Our findings add co-up-regulation by miRNA into miRNA regulatory networks and add a bidirectional twist to the impact miRNAs have on protein regulation and glycosylation.
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Affiliation(s)
| | - Joseph N. Reyes
- Department of Chemistry, University of Alberta, Edmonton, Canada
| | | | - Hoi Hei Ng
- Department of Chemistry, University of Alberta, Edmonton, Canada
| | - Dawn Macdonald
- Department of Chemistry, University of Alberta, Edmonton, Canada
| | - Eva Hernando
- Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA
- Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
| | - Lara K. Mahal
- Department of Chemistry, University of Alberta, Edmonton, Canada
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3
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Anvari S, Nikbakht M, Vaezi M, Amini-Kafiabad S, Ahmadvand M. Immune checkpoints and ncRNAs: pioneering immunotherapy approaches for hematological malignancies. Cancer Cell Int 2024; 24:410. [PMID: 39702293 DOI: 10.1186/s12935-024-03596-8] [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: 03/19/2024] [Accepted: 12/03/2024] [Indexed: 12/21/2024] Open
Abstract
Hematological malignancies are typically treated with chemotherapy and radiotherapy as the first-line conventional therapies. However, non-coding RNAs (ncRNAs) are a rapidly expanding field of study in cancer biology that influences the growth, differentiation, and proliferation of tumors by targeting immunological checkpoints. This study reviews the results of studies (from 2012 to 2024) that consider the immune checkpoints and ncRNAs in relation to hematological malignancies receiving immunotherapy. This article provides a summary of the latest advancements in immunotherapy for treating hematological malignancies, focusing on the role of immune checkpoints and ncRNAs in the immune response and their capacity for innovative strategies. The paper also discusses the function of immune checkpoints in maintaining immune homeostasis and how their dysregulation can contribute to developing leukemia and lymphoma. Finally, this research concludes with a discussion on the obstacles and future directions in this rapidly evolving field, emphasizing the need for continued research to fully harness the capacity of immune checkpoints and ncRNAs in immunotherapy for hematological malignancies.
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Affiliation(s)
- Samira Anvari
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Mohsen Nikbakht
- Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Vaezi
- Hematology, Oncology, and Stem Cell Transplantation Research Center Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sedigheh Amini-Kafiabad
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
| | - Mohammad Ahmadvand
- Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.
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Golovina E, Kokavec J, Kazantsev D, Yurikova O, Bajecny M, Savvulidi FG, Simersky R, Lenobel R, Tost J, Herynek V, Sefc L, Sebela M, Klener P, Zemanova Z, Stopka T, Vargova KS. Deficiency of miR-155 in leukemic B-cells results in cell cycle arrest and deregulation of MIR155HG/TP53INP1/CDKN1A/CCND1 network. Arch Med Res 2024; 56:103124. [PMID: 39591901 DOI: 10.1016/j.arcmed.2024.103124] [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: 01/04/2024] [Revised: 07/15/2024] [Accepted: 10/30/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
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Affiliation(s)
- Elena Golovina
- Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Juraj Kokavec
- Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, First Faculty of Medicine, Charles University, Vestec, Czech Republic
| | - Dmitry Kazantsev
- Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Oxana Yurikova
- Al-Farabi Kazakh National University, Faculty of Biology and Biotechnology, Almaty, Kazakhstan
| | - Martin Bajecny
- Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic; The Center for Advanced Preclinical Imaging, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Filipp Georgijevic Savvulidi
- Department of Animal Science, Faculty of Agrobiology, Food and Natural Resources, Czech University, Prague, Kamýcká, Czech Republic
| | - Radim Simersky
- Department of Chemical Biology, Faculty of Science, Palacký University, Olomouc, Czech Republic
| | - Rene Lenobel
- Laboratory of Growth Regulators, Institute of Experimental Botany of the Czech Academy of Sciences and Palacký University, Olomouc, Czech Republic
| | - Jorg Tost
- Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie Francois Jacob, Universite Paris-Saclay, Évry, France
| | - Vit Herynek
- The Center for Advanced Preclinical Imaging, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Ludek Sefc
- The Center for Advanced Preclinical Imaging, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Marek Sebela
- Department of Biochemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic
| | - Pavel Klener
- Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Zuzana Zemanova
- Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Tomas Stopka
- Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, First Faculty of Medicine, Charles University, Vestec, Czech Republic
| | - Karina Savvulidi Vargova
- Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
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5
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Koumpis E, Georgoulis V, Papathanasiou K, Papoudou-Bai A, Kanavaros P, Kolettas E, Hatzimichael E. The Role of microRNA-155 as a Biomarker in Diffuse Large B-Cell Lymphoma. Biomedicines 2024; 12:2658. [PMID: 39767565 PMCID: PMC11673977 DOI: 10.3390/biomedicines12122658] [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: 10/19/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL pathogenesis, since miR-155 regulates key pathways, transcription factors and cytokine expression and shapes the tumor microenvironment in DLBCL. In this review, we examine the role of miR-155 in DLBCL and its potential as a future diagnostic, prognostic, or predictive biomarker.
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Affiliation(s)
- Epameinondas Koumpis
- Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (E.K.); (V.G.); (K.P.)
| | - Vasileios Georgoulis
- Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (E.K.); (V.G.); (K.P.)
| | - Konstantina Papathanasiou
- Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (E.K.); (V.G.); (K.P.)
| | - Alexandra Papoudou-Bai
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece;
| | - Panagiotis Kanavaros
- Department of Anatomy-Histology-Embryology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Evangelos Kolettas
- Laboratory of Biology, Faculty of Medicine, School of Health Sciences, Institute of Biosciences, University Centre for Research and Innovation, University of Ioannina, 45110 Ioannina, Greece;
- Biomedical Research Institute, Foundation for Research and Technology, 45110 Ioannina, Greece
| | - Eleftheria Hatzimichael
- Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (E.K.); (V.G.); (K.P.)
- Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Lu D, Zhang Q, Zheng C, Li J, Yin Z. DGNMDA: Dual Heterogeneous Graph Neural Network Encoder for miRNA-Disease Association Prediction. Bioengineering (Basel) 2024; 11:1132. [PMID: 39593792 PMCID: PMC11591469 DOI: 10.3390/bioengineering11111132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/03/2024] [Accepted: 11/09/2024] [Indexed: 11/28/2024] Open
Abstract
In recent years, numerous studies have highlighted the pivotal importance of miRNAs in personalized healthcare, showcasing broad application prospects. miRNAs hold significant potential in disease diagnosis, prognosis assessment, and therapeutic target discovery, making them an integral part of precision medicine. They are expected to enable precise disease subtyping and risk prediction, thereby advancing the development of precision medicine. GNNs, a class of deep learning architectures tailored for graph data analysis, have greatly facilitated the advancement of miRNA-disease association prediction algorithms. However, current methods often fall short in leveraging network node information, particularly in utilizing global information while neglecting the importance of local information. Effectively harnessing both local and global information remains a pressing challenge. To tackle this challenge, we propose an innovative model named DGNMDA. Initially, we constructed various miRNA and disease similarity networks based on authoritative databases. Subsequently, we creatively design a dual heterogeneous graph neural network encoder capable of efficiently learning feature information between adjacent nodes and similarity information across the entire graph. Additionally, we develop a specialized fine-grained multi-layer feature interaction gating mechanism to integrate outputs from the neural network encoders to identify novel associations connecting miRNAs with diseases. We evaluate our model using 5-fold cross-validation and real-world disease case studies, based on the HMDD V3.2 dataset. Our method demonstrates superior performance compared to existing approaches in various tasks, confirming the effectiveness and potential of DGNMDA as a robust method for predicting miRNA-disease associations.
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Affiliation(s)
- Daying Lu
- School of Cyber Science and Engineering, Qufu Normal University, Qufu 273165, China; (Q.Z.); (C.Z.); (J.L.); (Z.Y.)
| | - Qi Zhang
- School of Cyber Science and Engineering, Qufu Normal University, Qufu 273165, China; (Q.Z.); (C.Z.); (J.L.); (Z.Y.)
| | - Chunhou Zheng
- School of Cyber Science and Engineering, Qufu Normal University, Qufu 273165, China; (Q.Z.); (C.Z.); (J.L.); (Z.Y.)
- Artificial Intelligence Academy, Anhui University, Hefei 230039, China
| | - Jian Li
- School of Cyber Science and Engineering, Qufu Normal University, Qufu 273165, China; (Q.Z.); (C.Z.); (J.L.); (Z.Y.)
| | - Zhe Yin
- School of Cyber Science and Engineering, Qufu Normal University, Qufu 273165, China; (Q.Z.); (C.Z.); (J.L.); (Z.Y.)
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Yu L, Peng Y, Sheng M, Wang Q, Jin Z, Huang J, Yang X. Electrochemical Biosensing Platform Based on Toehold-Mediated Strand Displacement Reaction and DSN Enzyme-Assisted Amplification for Two-Target Detection. ACS APPLIED MATERIALS & INTERFACES 2024; 16:45695-45703. [PMID: 39157906 DOI: 10.1021/acsami.4c08515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
Simultaneous detection of multiple targets is of great significance for accurate disease diagnosis. Herein, based on duplex-specific nuclease (DSN) assisted signal amplification and the toehold-mediated strand displacement reaction (TSDR), we constructed an electrochemical biosensor with high sensitivity and high specificity for dual-target detection. MiRNA-141 and miRNA-133a were used as the targets, and ferrocene (Fc) and methylene blue (MB) with significant peak potential differentiation were used as the electrochemical signal probes. The elaborately designed hairpin probe H1, which was fixed on the electrode surface, could be hybridized with the target miRNA-141 to perform signal amplification by the DSN-assisted enzyme cleavage cycle; thus, miRNA-141 could be detected by Fc signal changes at 0.41 V. The hairpin H1 can also combine with the MB-labeled signal probe (SP) output from miRNA-133a-induced TSDR, and the detection of miRNA-133a can be realized according to the response signal generated by MB at -0.26 V. The two sensing lines are independent of each other, and there is no mutual interference in the detection process. Therefore, two independent detection lines could be connected in series, and the simultaneous detection of two targets can be achieved on a single electrode. This novel detection strategy provides a new way to simultaneously detect different biomarkers.
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Affiliation(s)
- Linying Yu
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Yao Peng
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Mengting Sheng
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Qian Wang
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Zhiying Jin
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Jianshe Huang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
| | - Xiurong Yang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
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8
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Tili E, Otsu H, Commisso TL, Palamarchuk A, Balatti V, Michaille JJ, Nuovo GJ, Croce CM. MiR-155-targeted IcosL controls tumor rejection. Proc Natl Acad Sci U S A 2024; 121:e2408649121. [PMID: 38980909 PMCID: PMC11260163 DOI: 10.1073/pnas.2408649121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 06/08/2024] [Indexed: 07/11/2024] Open
Abstract
Elevated levels of miR-155 in solid and liquid malignancies correlate with aggressiveness of the disease. In this manuscript, we show that miR-155 targets transcripts encoding IcosL, the ligand for Inducible T-cell costimulator (Icos), thus impairing the ability of T cells to recognize and eliminate malignant cells. We specifically found that overexpression of miR-155 in B cells of Eµ-miR-155 mice causes loss of IcosL expression as they progress toward malignancy. Similarly, in mice where miR-155 expression is controlled by a Cre-Tet-OFF system, miR-155 induction led to malignant infiltrates lacking IcosL expression. Conversely, turning miR-155 OFF led to tumor regression and emergence of infiltrates composed of IcosL-positive B cells and Icos-positive T cells forming immunological synapses. Therefore, we next engineered malignant cells to express IcosL, in order to determine whether IcosL expression would increase tumor infiltration by cytotoxic T cells and reduce tumor progression. Indeed, overexpressing an IcosL-encoding cDNA in MC38 murine colon cancer cells before injection into syngeneic C57BL6 mice reduced tumor size and increased intratumor CD8+ T cell infiltration, that formed synapses with IcosL-expressing MC38 cells. Our results underscore the fact that by targeting IcosL transcripts, miR-155 impairs the infiltration of tumors by cytotoxic T cells, as well as the importance of IcosL on enhancing the immune response against malignant cells. These findings should lead to the development of more effective anticancer treatments based on maintaining, increasing, or restoring IcosL expression by malignant cells, along with impairing miR-155 activity.
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Affiliation(s)
- Esmerina Tili
- Department of Anesthesiology, Wexner Medical Center, College of Medicine, The Ohio State University, Columbus, OH43210
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | - Hajime Otsu
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | - Teresa L. Commisso
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | - Alexey Palamarchuk
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | - Veronica Balatti
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | - Jean-Jacques Michaille
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
| | | | - Carlo M. Croce
- The Ohio State University, Comprehensive Cancer Center, Department of Cancer Biology and Genetics, Wexner Medical Center, Columbus, OH43210
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Leng X, Zhang M, Xu Y, Wang J, Ding N, Yu Y, Sun S, Dai W, Xue X, Li N, Yang Y, Shi Z. Non-coding RNAs as therapeutic targets in cancer and its clinical application. J Pharm Anal 2024; 14:100947. [PMID: 39149142 PMCID: PMC11325817 DOI: 10.1016/j.jpha.2024.02.001] [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: 10/27/2023] [Revised: 01/12/2024] [Accepted: 02/01/2024] [Indexed: 08/17/2024] Open
Abstract
Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression. Oncogenes promote cell growth and proliferation, whereas tumor suppressor genes inhibit cell growth and division. The dysregulation of these genes can lead to the development of cancer. Recent studies have focused on non-coding RNAs (ncRNAs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), as therapeutic targets for cancer. In this article, we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets. Here, we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment. Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.
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Affiliation(s)
- Xuejiao Leng
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Mengyuan Zhang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yujing Xu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jingjing Wang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ning Ding
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yancheng Yu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Shanliang Sun
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weichen Dai
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xin Xue
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Nianguang Li
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ye Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zhihao Shi
- Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, 211198, China
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10
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Tsai YC, Chang CH, Chong YB, Wu CH, Tsai HP, Cheng TL, Lin CL. MicroRNA-195-5p Attenuates Intracerebral-Hemorrhage-Induced Brain Damage by Inhibiting MMP-9/MMP-2 Expression. Biomedicines 2024; 12:1373. [PMID: 38927580 PMCID: PMC11201846 DOI: 10.3390/biomedicines12061373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024] Open
Abstract
Intracerebral hemorrhage (ICH) remains a devastating disease with high mortality, and there is a lack of effective strategies to improve functional outcomes. The primary injury of ICH is mechanical damage to brain tissue caused by the hematoma. Secondary injury, resulting from inflammation, red cell lysis, and thrombin production, presents a potential target for therapeutic intervention. Inflammation, crucial in secondary brain injury, involves both cellular and molecular components. MicroRNAs (miRNAs) are vital regulators of cell growth, differentiation, and apoptosis. Their deregulation may lead to diseases, and modulating miRNA expression has shown therapeutic potential, especially in cancer. Recent studies have implicated miRNAs in the pathogenesis of stroke, affecting endothelial dysfunction, neurovascular integrity, edema, apoptosis, inflammation, and extracellular matrix remodeling. Preclinical and human studies support the use of miRNA-directed gene modulation as a therapeutic strategy for ICH. Our study focused on the effects of miR-195 in ICH models. Neurological tests, including the corner turn and grip tests, indicated that miR-195 treatment led to improvements in motor function impairments caused by ICH. Furthermore, miR-195-5p significantly reduced brain edema in the ipsilateral hemisphere and restored blood-brain barrier (BBB) integrity, as shown by reduced Evans blue dye extravasation. These results suggest miR-195-5p's potential in attenuating ICH-induced apoptosis, possibly related to its influence on MMP-9 and MMP-2 expression, enzymes associated with secondary brain injury. The anti-apoptotic effects of miR-195-5p, demonstrated through TUNEL assays, further underscore its therapeutic promise in addressing the secondary brain injury and apoptosis associated with ICH. In conclusion, miR-195-5p demonstrates a significant neuroprotective effect against ICH-induced neural damage, brain edema, and BBB disruption, primarily through the downregulation of MMP-9 and MMP-2. Our findings indicate that miR-195-5p holds therapeutic potential in managing cerebral cell death following ICH.
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Affiliation(s)
- Yi-Cheng Tsai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (Y.-C.T.); (C.-H.C.); (Y.B.C.)
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
| | - Chih-Hui Chang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (Y.-C.T.); (C.-H.C.); (Y.B.C.)
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
| | - Yoon Bin Chong
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (Y.-C.T.); (C.-H.C.); (Y.B.C.)
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
| | - Chieh-Hsin Wu
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
- Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hung-Pei Tsai
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Tian-Lu Cheng
- Department of Biochemistry, School of Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chih-Lung Lin
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (Y.-C.T.); (C.-H.C.); (Y.B.C.)
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.W.); (H.-P.T.)
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11
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Bahashwan S, Alsaadi M, Barefah A, Almahdi H, Alahwal H, Almohammadi A, Radhwi O, Daous Y, Idrees S, Almehdar H, Qadri I. Profiling of microRNAs by next-generation sequencing: Potential biomarkers for diffuse large B-cell lymphoma. J Taibah Univ Med Sci 2024; 19:619-627. [PMID: 38812724 PMCID: PMC11133910 DOI: 10.1016/j.jtumed.2024.04.010] [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: 10/26/2023] [Revised: 03/27/2024] [Accepted: 04/28/2024] [Indexed: 05/31/2024] Open
Abstract
Background Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs) are associated with most non-Hodgkin lymphomas. Non-coding microRNAs (miRNAs) greatly affect gene expression. A single miRNA can target numerous genes, thus largely influencing gene expression networks. MiRNAs can act as oncogenes or tumor suppressors in controlling DLBCL progression. This study investigated the roles of miRNAs in patients with DLBCL through next-generation sequencing, which was found to be sensitive, accurate, and robust. Methods The study involved seven patients with DLBCLs and three controls at a hematology-oncology clinic. MiRNA was extracted from existing formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Illumina next-generation sequencing was used to sequence samples for miRNA profiling. Results Samples from patients showed expression of various hsa-mir miRNAs (1248, 3607, 21, 142, 1244, 182, 6516, 766, 1291, 4449, and 181a), whereas those from healthy individuals showed expression of hsa-mir 1248, 3607, 21, 142, and 877. Hsa-mir-877-3p is known to target multiple genes, and miRNAs such as hsa-mir-877-3p, hsa-mir-1291, and hsa-mir-181a-5p interact primarily with target genes. Conclusions MiRNA profiling in FFPE tissues from patients with DLBCL suggested that miRNA levels can distinguish patients with DLBCL from controls, and therefore may provide prognostic or diagnostic biomarkers for DLBCL. Altered genes and miRNAs may also be potential therapeutic targets.
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Affiliation(s)
- Salem Bahashwan
- Hematology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
| | - Mohammed Alsaadi
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, KSA
| | - Ahmed Barefah
- Hematology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
| | - Hadiah Almahdi
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, KSA
- Research and Development Unit, Al Borg Diagnostics, Jeddah, KSA
| | - Hatem Alahwal
- Hematology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
| | - Abdullah Almohammadi
- Hematology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
| | - Osman Radhwi
- Hematology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
| | - Yara Daous
- Hematology Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA
| | - Sherif Idrees
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, KSA
- Research and Development Unit, Al Borg Diagnostics, Jeddah, KSA
| | - Hussien Almehdar
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, KSA
| | - Ishtiaq Qadri
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, KSA
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12
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Shen M, Chen T, Li X, Zhao S, Zhang X, Zheng L, Qian B. The role of miR-155 in urologic malignancies. Biomed Pharmacother 2024; 174:116412. [PMID: 38520867 DOI: 10.1016/j.biopha.2024.116412] [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: 11/19/2023] [Revised: 02/28/2024] [Accepted: 03/06/2024] [Indexed: 03/25/2024] Open
Abstract
MicroRNAs (miRNAs) are a class of short non-coding RNAs that play a crucial role in regulating gene expression across multiple levels. They are involved in a wide range of physiological processes, including proliferation, differentiation, apoptosis, and cell cycle control. In recent years, miRNAs have emerged as pivotal regulatory molecules in the development and progression of tumors. Among these, miR-155 has garnered significant attention due to its high expression in various diseases, particularly urologic malignancies. Since an extensive corpus of studies having focused on the roles of miR-155 in various urologic malignancies, it is essential to summarize the current evidence on this topic through a comprehensive review. Altered miR-155 expression is related to various physiological and pathological processes, including immune response, inflammation, tumor development and treatment resistance. Notably, alterations in miR-155 expression have been observed in urologic malignancies as well. The up-regulation of miR-155 expression is commonly observed in urologic malignancies, contributing to their progression by targeting specific proteins and signaling pathways. This article provides a comprehensive review of the significant role played by miR-155 in the development of urologic malignancies. Furthermore, the potential of miR-155 as a biomarker and therapeutic target in urologic malignancies is also discussed.
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Affiliation(s)
- Maolei Shen
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, China
| | - Tao Chen
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi 341000, China; Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China; Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi 341000, China
| | - Xin Li
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, China
| | - Shankun Zhao
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, China
| | - Xinsheng Zhang
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang 318000, China
| | - Liying Zheng
- Postgraduate Department, First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China.
| | - Biao Qian
- Department of Urology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China; Key Laboratory of Urology and Andrology of Ganzhou, Ganzhou, Jiangxi 341000, China.
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13
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Deng L, Chen X, Ma P, Wu Y, Okoye CO, Du D, Deng Q. The combined effect of oxidative stress and TRPV1 on temperature-induced asthma: Evidence in a mouse model. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 344:123313. [PMID: 38185356 DOI: 10.1016/j.envpol.2024.123313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 12/17/2023] [Accepted: 01/04/2024] [Indexed: 01/09/2024]
Abstract
Temperature is one of the possible activators for asthma. As global warming continues, the health hazard of high temperatures is increasing. It is unclear, nevertheless, how high temperatures affect asthma. The research aims to examine how asthma is affected by high temperatures and underlying molecular mechanisms. The BALB/c mice were adopted in a model of asthma. The mice were exposed at 24 °C, 38 °C and 40 °C for 4h on weekdays from day 1 to day 30. After the experiment, the lung function was measured in vivo, and then serum protein, pulmonary inflammation and immunohistochemistry assay was assessed in vitro. As the temperature increased from 24 °C to 40 °C, there was a significant increase in serum protein, while there is no discernible difference in serum protein of OVA-sIgE and OVA-sIgG between the OVA (38 °C) group and OVA (24 °C) group. The immunohistochemistry assay showed a change in the pro-inflammatory cytokines. The histopathological analysis exhibited the change of airway structure after high-temperature exposure, especially for exposure at 40 °C. The results of signals protein showed a remarkable rise of TRPV1 for OVA+40 °C. Our results revealed that high temperatures may make asthmatic airway dysfunction severe, and the higher the temperature, the more serious asthma. The oxidative stress and TRPV1 receptor can be a potential drug target for asthma. It will provide a new tool for precision medicine in asthma.
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Affiliation(s)
- Linjing Deng
- School of Emergency Management, Jiangsu University, 212000, Zhenjiang, China; School of environment and safety engineering, Jiangsu University, 212000, Zhenjiang, China.
| | - Xunfeng Chen
- Biofuels Institute of Jiangsu university, Jiangsu University, 212000, Zhenjiang, China; School of environment and safety engineering, Jiangsu University, 212000, Zhenjiang, China
| | - Ping Ma
- Laboratory of Environment-Immunological and Neurological Diseases, Hubei University of Science and Technology, Xianning, 437100, China
| | - Yang Wu
- Laboratory of Environment-Immunological and Neurological Diseases, Hubei University of Science and Technology, Xianning, 437100, China
| | - Charles Obinwanne Okoye
- School of environment and safety engineering, Jiangsu University, 212000, Zhenjiang, China; Department of Zoology & Environmental Biology, University of Nigeria, Nsukka, 410001, Nigeria
| | - Daolin Du
- School of Emergency Management, Jiangsu University, 212000, Zhenjiang, China; School of environment and safety engineering, Jiangsu University, 212000, Zhenjiang, China
| | - Qihong Deng
- School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
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14
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Zhang Y, Guo W, Zhan Z, Bai O. Carcinogenic mechanisms of virus-associated lymphoma. Front Immunol 2024; 15:1361009. [PMID: 38482011 PMCID: PMC10932979 DOI: 10.3389/fimmu.2024.1361009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 02/12/2024] [Indexed: 04/17/2024] Open
Abstract
The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.
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Affiliation(s)
| | | | | | - Ou Bai
- Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China
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15
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Ali A, Mahla SB, Reza V, Hossein A, Bahareh K, Mohammad H, Fatemeh S, Mostafa AB, Leili R. MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia. EJHAEM 2024; 5:191-205. [PMID: 38406506 PMCID: PMC10887358 DOI: 10.1002/jha2.849] [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: 06/26/2023] [Revised: 12/13/2023] [Accepted: 12/29/2023] [Indexed: 02/27/2024]
Abstract
Small noncoding ribonucleic acids called microRNAs coordinate numerous critical physiological and biological processes such as cell division, proliferation, and death. These regulatory molecules interfere with the function of many genes by binding the 3'-UTR region of target mRNAs to inhibit their translation or even degrade them. Given that a large proportion of miRNAs behave as either tumor suppressors or oncogenes, any genetic or epigenetic aberration changeing their structure and/or function could initiate tumor formation and development. An example of such cancers is chronic lymphocytic leukemia (CLL), the most prevalent adult leukemia in Western nations, which is caused by unregulated growth and buildup of defective cells in the peripheral blood and lymphoid organs. Genetic alterations at cellular and molecular levels play an important role in the occurrence and development of CLL. In this vein, it was noted that the development of this disease is noticeably affected by changes in the expression and function of miRNAs. Many studies on miRNAs have shown that these molecules are pivotal in the prognosis of different cancers, including CLL, and their epigenetic alterations (e.g., methylation) can predict disease progression and response to treatment. Furthermore, miRNAs are involved in the development of drug resistance in CLL, and targeting these molecules can be considered a new therapeutic approach for the treatment of this disease. MiRNA screening can offer important information on the etiology and development of CLL. Considering the importance of miRNAs in gene expression regulation, their application in the diagnosis, prognosis, and treatment of CLL is reviewed in this paper.
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Affiliation(s)
- Afgar Ali
- Research Center for Hydatid Disease in IranKerman University of Medical SciencesKermanIran
| | - Sattarzadeh Bardsiri Mahla
- Stem Cells and Regenerative Medicine Innovation CenterKerman University of Medical SciencesKermanIran
- Department of Hematology and Laboratory Sciences, Faculty of Allied Medical SciencesKerman University of Medical SciencesKermanIran
| | - Vahidi Reza
- Research Center for Hydatid Disease in IranKerman University of Medical SciencesKermanIran
| | - Arezoomand Hossein
- Department of Hematology and Laboratory Sciences, Faculty of Allied Medical SciencesKerman University of Medical SciencesKermanIran
| | - Kashani Bahareh
- Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
| | - Hosseininaveh Mohammad
- Research Center for Hydatid Disease in IranKerman University of Medical SciencesKermanIran
| | - Sharifi Fatemeh
- Research Center of Tropical and Infectious DiseasesKerman University of Medical SciencesKermanIran
| | - Amopour Bahnamiry Mostafa
- Department of Research and Development, Production and Research ComplexPasteur Institute of IranTehranIran
| | - Rouhi Leili
- Student Research CommitteeKerman University of Medical SciencesKermanIran
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16
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Karimi B, Mokhtari K, Rozbahani H, Peymani M, Nabavi N, Entezari M, Rashidi M, Taheriazam A, Ghaedi K, Hashemi M. Pathological roles of miRNAs and pseudogene-derived lncRNAs in human cancers, and their comparison as prognosis/diagnosis biomarkers. Pathol Res Pract 2024; 253:155014. [PMID: 38128189 DOI: 10.1016/j.prp.2023.155014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 12/02/2023] [Accepted: 12/02/2023] [Indexed: 12/23/2023]
Abstract
This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.
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Affiliation(s)
- Bahareh Karimi
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Khatere Mokhtari
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Hossein Rozbahani
- Department of Psychology, North Tehran Branch, Islamic Azad University, Tehran, Iran; Department of Psychology, West Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Peymani
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H3Z6, Canada
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Afshin Taheriazam
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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17
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Pandey C, Tiwari P. Differential microRNAs Expression during Cancer Development, and Chemoprevention by Natural Compounds: A Comprehensive Review. J Environ Pathol Toxicol Oncol 2024; 43:65-80. [PMID: 39016142 DOI: 10.1615/jenvironpatholtoxicoloncol.2024050357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024] Open
Abstract
MicroRNAs are short non-coding RNAs that inhibit gene expression at the post-transcriptional level. Abnormal microRNA expression has been associated with different human diseases, including cancer. Epigenetic changes, mutation, transcriptional deregulation, DNA copy number abnormalities, and defects in the biogenesis machinery play an important role in abnormal microRNA expression. Modulation of microRNAs by natural agents has emerged to enhance the efficacy of conventional chemotherapy through combinatorial therapeutic approach. This review summarizes the current understanding of abnormal microRNA expression in cancer, the different cellular mechanisms of microRNA, and their prevention by natural compounds. Understanding microRNA expression patterns during cancer development may help to identify stage-specific molecular markers. Natural compounds that exert regulatory effects by modulating microRNAs can be used in better cancer chemopreventive strategies by directly targeting microRNAs or as a way to increase sensitivity to existing chemotherapy regimens.
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Affiliation(s)
- Chhaya Pandey
- School of Environmental Biology, Awadhesh Pratap Singh University, Rewa-486001, Madhya Pradesh, India
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18
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Pawar P, Gokavi J, Wakhare S, Bagul R, Ghule U, Khan I, Ganu V, Mukherjee A, Shete A, Rao A, Saxena V. MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors. Viruses 2023; 15:2206. [PMID: 38005883 PMCID: PMC10675553 DOI: 10.3390/v15112206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/28/2023] [Accepted: 10/02/2023] [Indexed: 11/26/2023] Open
Abstract
HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined. Since the progressors showed a dysregulated TLR-mediated innate response, we investigated the role of TLR agonists in restoring the innate functions of the progressors. The stimulation of PBMCs with TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 and TLR9 agonist-ODN 2216 resulted in an increased expression of IFN-α, IFN-β and IL-6. Interestingly, the expression of IFITM3, BST-2, IFITM-3, IFI-16 was also increased upon stimulation with TLR3 and TLR7 agonists, respectively. To further understand the molecular mechanism involved, the role of miR-155 was explored. Increased miR-155 expression was noted among the progressors. MiR-155 inhibition upregulated the expression of TLR3, NF-κB, IRF-3, TNF-α and the APOBEC-3G, IFITM-3, IFI-16 and BST-2 genes in the PBMCs of the progressors. To conclude, miR-155 negatively regulates TLR-mediated cytokines as wel l as the expression of host restriction factors, which play an important role in mounting anti-HIV responses; hence, targeting miR-155 might be helpful in devising strategic approaches towards alleviating HIV disease progression.
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Affiliation(s)
- Puja Pawar
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
| | - Jyotsna Gokavi
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
| | - Shilpa Wakhare
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
| | - Rajani Bagul
- Division of Clinical Sciences, ICMR-National AIDS Research Institute, Pune 411026, India; (R.B.); (U.G.); (A.R.)
| | - Ujjwala Ghule
- Division of Clinical Sciences, ICMR-National AIDS Research Institute, Pune 411026, India; (R.B.); (U.G.); (A.R.)
| | - Ishrat Khan
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India; (I.K.); (A.M.)
| | - Varada Ganu
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
| | - Anupam Mukherjee
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India; (I.K.); (A.M.)
| | - Ashwini Shete
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
| | - Amrita Rao
- Division of Clinical Sciences, ICMR-National AIDS Research Institute, Pune 411026, India; (R.B.); (U.G.); (A.R.)
| | - Vandana Saxena
- Division of Immunology and Serology, ICMR-National AIDS Research Institute, Pune 411026, India; (P.P.); (J.G.); (S.W.); (V.G.); (A.S.)
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19
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Panicker S, Chengizkhan G, Gor R, Ramachandran I, Ramalingam S. Exploring the Relationship between Fusion Genes and MicroRNAs in Cancer. Cells 2023; 12:2467. [PMID: 37887311 PMCID: PMC10605240 DOI: 10.3390/cells12202467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/05/2023] [Accepted: 10/12/2023] [Indexed: 10/28/2023] Open
Abstract
Fusion genes are key cancer driver genes that can be used as potential drug targets in precision therapies, and they can also serve as accurate diagnostic and prognostic biomarkers. The fusion genes can cause microRNA (miRNA/miR) aberrations in many types of cancer. Nevertheless, whether fusion genes incite miRNA aberrations as one of their many critical oncogenic functionalities for driving carcinogenesis needs further investigation. Recent discoveries of miRNA genes that are present within the regions of genomic rearrangements that initiate fusion gene-based intronic miRNA dysregulation have brought the fusion genes into the limelight and revealed their unexplored potential in the field of cancer biology. Fusion gene-based 'promoter-switch' event aberrantly activate the miRNA-related upstream regulatory signals, while fusion-based coding region alterations disrupt the original miRNA coding loci. Fusion genes can potentially regulate the miRNA aberrations regardless of the protein-coding capability of the resultant fusion transcript. Studies on out-of-frame fusion and nonrecurrent fusion genes that cause miRNA dysregulation have attracted the attention of researchers on fusion genes from an oncological perspective and therefore could have potential implications in cancer therapies. This review will provide insights into the role of fusion genes and miRNAs, and their possible interrelationships in cancer.
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Affiliation(s)
- Saurav Panicker
- Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, Tamil Nadu, India; (S.P.); (R.G.)
| | - Gautham Chengizkhan
- Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India;
| | - Ravi Gor
- Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, Tamil Nadu, India; (S.P.); (R.G.)
| | - Ilangovan Ramachandran
- Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India;
| | - Satish Ramalingam
- Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, Tamil Nadu, India; (S.P.); (R.G.)
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20
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Gu F, Huang X, Huang W, Zhao M, Zheng H, Wang Y, Chen R. The role of miRNAs in Behçet's disease. Front Immunol 2023; 14:1249826. [PMID: 37860009 PMCID: PMC10584330 DOI: 10.3389/fimmu.2023.1249826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/12/2023] [Indexed: 10/21/2023] Open
Abstract
The symptoms of Behçet's disease (BD), a multisystemic condition with autoimmune and inflammation as hallmarks, include arthritis, recurring oral and vaginal ulcers, skin rashes and lesions, and involvement of the nervous, gastrointestinal, and vascular systems. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), may be important regulators of inflammation and autoimmune disease. These ncRNAs are essential to the physiological and pathophysiological disease course, and miRNA in particular has received significant attention for its role and function in BD and its potential use as a diagnostic biomarker in recent years. Although promising as therapeutic targets, miRNAs must be studied further to fully comprehend how miRNAs in BD act biologically.
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Affiliation(s)
| | | | | | | | | | - Yuanyin Wang
- College and Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
| | - Ran Chen
- College and Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, China
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21
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Moutabian H, Radi UK, Saleman AY, Adil M, Zabibah RS, Chaitanya MNL, Saadh MJ, Jawad MJ, Hazrati E, Bagheri H, Pal RS, Akhavan-Sigari R. MicroRNA-155 and cancer metastasis: Regulation of invasion, migration, and epithelial-to-mesenchymal transition. Pathol Res Pract 2023; 250:154789. [PMID: 37741138 DOI: 10.1016/j.prp.2023.154789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 08/24/2023] [Accepted: 09/01/2023] [Indexed: 09/25/2023]
Abstract
Among the leading causes of death globally has been cancer. Nearly 90% of all cancer-related fatalities are attributed to metastasis, which is the growing of additional malignant growths out of the original cancer origin. Therefore, a significant clinical need for a deeper comprehension of metastasis exists. Beginning investigations are being made on the function of microRNAs (miRNAs) in the metastatic process. Tiny non-coding RNAs called miRNAs have a crucial part in controlling the spread of cancer. Some miRNAs regulate migration, invasion, colonization, cancer stem cells' properties, the epithelial-mesenchymal transition (EMT), and the microenvironment, among other processes, to either promote or prevent metastasis. One of the most well-conserved and versatile miRNAs, miR-155 is primarily distinguished by overexpression in a variety of illnesses, including malignant tumors. It has been discovered that altered miR-155 expression is connected to a number of physiological and pathological processes, including metastasis. As a result, miR-155-mediated signaling pathways were identified as possible cancer molecular therapy targets. The current research on miR-155, which is important in controlling cancer cells' invasion, and metastasis as well as migration, will be summarized in the current work. The crucial significance of the lncRNA/circRNA-miR-155-mRNA network as a crucial regulator of carcinogenesis and a player in the regulation of signaling pathways or related genes implicated in cancer metastasis will be covered in the final section. These might provide light on the creation of fresh treatment plans for controlling cancer metastasis.
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Affiliation(s)
- Hossein Moutabian
- Radiation Sciences Research Center (RSRC), AJA University of Medical Sciences, Tehran, Iran
| | - Usama Kadem Radi
- College of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq
| | | | | | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Mv N L Chaitanya
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India
| | - Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan; Applied Science Research Center. Applied Science Private University, Amman, Jordan
| | | | - Ebrahi Hazrati
- Trauma Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Hamed Bagheri
- Radiation Sciences Research Center (RSRC), AJA University of Medical Sciences, Tehran, Iran; Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Rashmi Saxena Pal
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144402, India
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center, Tuebingen, Germany; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University, Warsaw, Poland
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22
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Autore F, Ramassone A, Stirparo L, Pagotto S, Fresa A, Innocenti I, Visone R, Laurenti L. Role of microRNAs in Chronic Lymphocytic Leukemia. Int J Mol Sci 2023; 24:12471. [PMID: 37569845 PMCID: PMC10419063 DOI: 10.3390/ijms241512471] [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: 07/05/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia in adults, with a highly variable clinical course. Improvement in the knowledge of the molecular pathways behind this disease has led to the development of increasingly specific therapies, such as BCR signaling inhibitors and BCL-2 inhibitors. In this context, the emerging role of microRNAs (miRNAs) in CLL pathophysiology and their possible application in therapy is worth noting. MiRNAs are one of the most important regulatory molecules of gene expression. In CLL, they can act both as oncogenes and tumor suppressor genes, and the deregulation of specific miRNAs has been associated with prognosis, progression, and drug resistance. In this review, we describe the role of the miRNAs that primarily impact the disease, and how these miRNAs could be used as therapeutic tools. Certainly, the use of miRNAs in clinical practice is still limited in CLL. Many issues still need to be solved, particularly regarding their biological and safety profile, even if several studies have suggested their efficacy on the disease, alone or in combination with other drugs.
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Affiliation(s)
- Francesco Autore
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy (A.F.); (I.I.); (L.L.)
| | - Alice Ramassone
- Center for Advanced Studies and Technology (CAST), G. d’Annunzio University, 66100 Chieti, Italy; (A.R.); (S.P.); (R.V.)
| | - Luca Stirparo
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy (A.F.); (I.I.); (L.L.)
| | - Sara Pagotto
- Center for Advanced Studies and Technology (CAST), G. d’Annunzio University, 66100 Chieti, Italy; (A.R.); (S.P.); (R.V.)
- Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University, 66100 Chieti, Italy
| | - Alberto Fresa
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy (A.F.); (I.I.); (L.L.)
| | - Idanna Innocenti
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy (A.F.); (I.I.); (L.L.)
| | - Rosa Visone
- Center for Advanced Studies and Technology (CAST), G. d’Annunzio University, 66100 Chieti, Italy; (A.R.); (S.P.); (R.V.)
- Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University, 66100 Chieti, Italy
| | - Luca Laurenti
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy (A.F.); (I.I.); (L.L.)
- Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
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23
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Wu S, Wu Y, Deng S, Lei X, Yang X. Emerging roles of noncoding RNAs in human cancers. Discov Oncol 2023; 14:128. [PMID: 37439905 DOI: 10.1007/s12672-023-00728-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 06/14/2023] [Indexed: 07/14/2023] Open
Abstract
Studies have found that RNA encoding proteins only account for a small part of the total number, most RNA is non-coding RNA, and non-coding RNA may affect the occurrence and development of human cancers by affecting gene expression, therefore play an important role in human pathology. At present, ncRNAs studied include miRNA, circRNA, lncRNA, piRNA, and snoRNA, etc. After decades of research, the basic role of these ncRNAs in many cancers has been clear. As far as we know, the role of miRNAs in cancer is one of the hottest research directions, however, it is also found that the imbalance of ncRNAs will affect the occurrence of gastric cancer, breast cancer, lung cancer, meanwhile, it may also affect the prognosis of these cancers. Therefore, the study of ncRNAs in cancers may help to find new cancer diagnostic and treatment methods. Here, we reviewed the biosynthesis and characteristics of miRNA, cricRNA, and lncRNA etc., their roles in human cancers, as well as the mechanism through which these ncRNAs affect human cancers.
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Affiliation(s)
- Shijie Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Yiwen Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Sijun Deng
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.
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24
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Kim T, Croce CM. MicroRNA: trends in clinical trials of cancer diagnosis and therapy strategies. Exp Mol Med 2023; 55:1314-1321. [PMID: 37430087 PMCID: PMC10394030 DOI: 10.1038/s12276-023-01050-9] [Citation(s) in RCA: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 05/22/2023] [Accepted: 06/02/2023] [Indexed: 07/12/2023] Open
Abstract
As a type of short noncoding RNAs, microRNA (miRNA) undoubtedly plays a crucial role in cancer development. Since the discovery of the identity and clinical functions of miRNAs, over the past few decades, the roles of miRNAs in cancer have been actively investigated. Numerous pieces of evidence indicate that miRNAs are pivotal factors in most types of cancer. Recent cancer research focused on miRNAs has identified and characterized a large cohort of miRNAs commonly dysregulated in cancer or exclusively dysregulated in specific types of cancer. These studies have suggested the potential of miRNAs as biomarkers in the diagnosis and prognostication of cancer. Moreover, many of these miRNAs have oncogenic or tumor-suppressive functions. MiRNAs have been the focus of research given their potential clinical applications as therapeutic targets. Currently, various oncology clinical trials using miRNAs in screening, diagnosis, and drug testing are underway. Although clinical trials studying miRNAs in various diseases have been reviewed before, there have been fewer clinical trials related to miRNAs in cancer. Furthermore, updated results of recent preclinical studies and clinical trials of miRNA biomarkers and drugs in cancer are needed. Therefore, this review aims to provide up-to-date information on miRNAs as biomarkers and cancer drugs in clinical trials.
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Affiliation(s)
- Taewan Kim
- Department of Anatomy, Histology & Developmental Biology, International Cancer Center, School of Medicine, Shenzhen University, Shenzhen, China.
| | - Carlo M Croce
- Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
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25
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Studies on the application of single-stranded DNA and PNA probes for electrochemical detection of miRNA 141. Bioelectrochemistry 2023; 150:108363. [PMID: 36608369 DOI: 10.1016/j.bioelechem.2022.108363] [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: 04/06/2022] [Revised: 12/09/2022] [Accepted: 12/28/2022] [Indexed: 12/31/2022]
Abstract
The abnormal concentration of microRNAs (miRNAs) can be associated with occurrence of various diseases including cancer, cardiovascular and neurodegenerative, hence they can be considered as potential biomarkers. An attractive approach could be the application of electrochemical methods, particularly where hybridization event between single-stranded deoxyribonucleic acid (ssDNA) or peptide-nucleic acid (PNA) with miRNA strand happens. Recently, the use of various nanomaterials such as gold nanoparticles, graphene oxide, quantum dots as well as catalyzed hairpin assembly or hybridization chain reaction were proposed to further enhance the performance of elaborated sensors. Herein, we present the studies on selection of receptor layer composition for detection of miRNA 141. The possibility of formation of receptor layer and further duplex monolayer between ssDNA or PNA with miRNA was analyzed by atomic force microscopy (AFM) technique. The interaction of ssDNA and PNA probes with miRNA was further verified using surface plasmon resonance (SPR) and quartz - crystal microbalance (QCM) techniques. On the basis of impedance spectroscopy it was shown that the use of unlabelled ssDNA as receptor layer provided 0.1 pM detection limit. This shows that proposed biosensor that is simple in preparation and use is an attractive alternative to other recently presented approaches.
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26
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Ehm P, Bettin B, Jücker M. Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119467. [PMID: 36958526 DOI: 10.1016/j.bbamcr.2023.119467] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 03/03/2023] [Accepted: 03/12/2023] [Indexed: 03/25/2023]
Abstract
Within the various subtypes of ALL, patients with a BCR-ABL-positive background as well as with a genetic change in the KMT2A gene have by far the worst survival probabilities. Interestingly, both subtypes are characterized by highly activated tyrosine kinases. SHIP1 serves as an important negative regulator of the PI3K/AKT signaling pathway, which is often constitutively activated in ALL. The protein expression of SHIP1 is decreased in most T-ALL and in some subgroups of B-ALL. In this study, we analyzed the expression of SHIP1 protein in detail in the context of groups with aberrant activated tyrosine kinases, namely BCR-ABL (Ph+) and Flt3 (KMT2A translocations). We demonstrate that constitutively activated Src kinases downstream of BCR-ABL and receptor tyrosine kinases reduce the SHIP1 expression in a SHIP1-Y1021 phosphorylated-dependent manner with subsequent ubiquitin marked proteasomal degradation. Inhibition of BCR-ABL (Imatinib), Flt3 (Quizartinib) or Src-Kinase-Family (Saracatinib) leads to significant reconstitution of SHIP1 protein expression. These results further support a functional role of SHIP1 as tumor suppressor protein and could be the basis for the establishment of a targeted therapy form.
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Affiliation(s)
- Patrick Ehm
- Institute of Biochemistry and Signal Transduction, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; Research Institute Children's Cancer Center Hamburg, Hamburg and Dept. of Pediatric Oncology and Hematology, University Medical Center, Hamburg, Germany.
| | - Bettina Bettin
- Institute of Biochemistry and Signal Transduction, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
| | - Manfred Jücker
- Institute of Biochemistry and Signal Transduction, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
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27
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Zhao A, Zhou H, Yang J, Li M, Niu T. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies. Signal Transduct Target Ther 2023; 8:71. [PMID: 36797244 PMCID: PMC9935927 DOI: 10.1038/s41392-023-01342-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 01/03/2023] [Accepted: 01/19/2023] [Indexed: 02/18/2023] Open
Abstract
Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lymphoma. Furthermore, the hypomethylating agents and histone deacetylase inhibitors are effective to treat acute myeloid leukemia and T-cell lymphomas, indicating that epigenetic regulation is indispensable to hematologic oncogenesis. Epigenetic regulation mainly includes DNA modifications, histone modifications, and noncoding RNA-mediated targeting, and regulates various DNA-based processes. This review presents the role of writers, readers, and erasers of DNA methylation and histone methylation, and acetylation in hematologic malignancies. In addition, this review provides the influence of microRNAs and long noncoding RNAs on hematologic malignancies. Furthermore, the implication of epigenetic regulation in targeted treatment is discussed. This review comprehensively presents the change and function of each epigenetic regulator in normal and oncogenic hematopoiesis and provides innovative epigenetic-targeted treatment in clinical practice.
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Affiliation(s)
- Ailin Zhao
- Department of Hematology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Hui Zhou
- Department of Hematology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Jinrong Yang
- Department of Hematology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Meng Li
- Department of Hematology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China
| | - Ting Niu
- Department of Hematology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
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28
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Wang Y, Li Q, Wang S, Wang BJ, Jin Y, Hu H, Fu QS, Wang JW, Wu Q, Qian L, Cao TT, Xia YB, Huang XX, Xu L. The role of noncoding RNAs in cancer lipid metabolism. Front Oncol 2022; 12:1026257. [PMID: 36452489 PMCID: PMC9704363 DOI: 10.3389/fonc.2022.1026257] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/20/2022] [Indexed: 12/03/2023] Open
Abstract
Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.
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Affiliation(s)
- Ye Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Qian Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Song Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Bi-jun Wang
- Department of Clinical Medicine, Clinical College of Anhui Medical University, Hefei, Anhui, China
| | - Yan Jin
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Hao Hu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Qing-sheng Fu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Jia-wei Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Qing Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Long Qian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Ting-ting Cao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Ya-bin Xia
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Xiao-xu Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
| | - Li Xu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China
- Non-coding RNA Research Center of Wannan Medical College, Yijishan Hospital, Wuhu, Anhui, China
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Menegatti J, Nakel J, Stepanov YK, Caban KM, Ludwig N, Nord R, Pfitzner T, Yazdani M, Vilimova M, Kehl T, Lenhof HP, Philipp SE, Meese E, Fröhlich T, Grässer FA, Hart M. Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma. Cancers (Basel) 2022; 14:cancers14205031. [PMID: 36291816 PMCID: PMC9600116 DOI: 10.3390/cancers14205031] [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: 09/15/2022] [Revised: 10/10/2022] [Accepted: 10/11/2022] [Indexed: 11/22/2022] Open
Abstract
Simple Summary The gene of the human tumor suppressive microRNA-142 (miR-142) carries mutations in about 20% of cases of diffuse large B-cell lymphoma (DLBCL). Because microRNAs post-transcriptionally regulate the protein expression of their cognate messenger RNA (mRNAs) targets, we determined the effect of miR-142 knockout on protein expression in two cell lines derived from DLBCL. We found a significant up-regulation of 52 proteins but also a down-regulation of 41 proteins upon miR-142 deletion. Knockout of a miRNA may be used to identify novel targets, and seed-sequence mutants of a miRNA unable to bind to their targets can be used to confirm potential novel targets. With this approach, we identify AKT1S1, CCNB1, LIMA1 and TFRC as novel targets of miR-142. As miR-142 is highly present in the miRNA processing RISC complexes, the deletion of this miRNA might result in its replacement by other miRNAs, thus introducing an additional layer of complexity regarding gene regulation. Abstract Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines. Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL. Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. Conclusions: Seed-sequence mutants of miR-142 confirmed potential targets and novel targets of miRNAs can be identified in miRNA knockout cell lines. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when miRNAs highly present in RISC complexes are replaced by other miRNAs, primary effects on gene expression may be covered by secondary layers of regulation.
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Affiliation(s)
- Jennifer Menegatti
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Jacqueline Nakel
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Youli K. Stepanov
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Karolina M. Caban
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Nicole Ludwig
- Institute of Human Genetics, Saarland University, 66421 Homburg, Germany
| | - Ruth Nord
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Thomas Pfitzner
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Maryam Yazdani
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Monika Vilimova
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
| | - Tim Kehl
- Center for Bioinformatics, Saarland University, 66041 Saarbrücken, Germany
| | - Hans-Peter Lenhof
- Center for Bioinformatics, Saarland University, 66041 Saarbrücken, Germany
| | - Stephan E. Philipp
- Experimental and Clinical Pharmacology and Toxicology, Saarland University Medical School, 66421 Homburg, Germany
| | - Eckart Meese
- Institute of Human Genetics, Saarland University, 66421 Homburg, Germany
| | - Thomas Fröhlich
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
| | - Friedrich A. Grässer
- Institute of Virology, Saarland University Medical School, 66421 Homburg, Germany
- Correspondence: (F.A.G.); (M.H.)
| | - Martin Hart
- Institute of Human Genetics, Saarland University, 66421 Homburg, Germany
- Correspondence: (F.A.G.); (M.H.)
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30
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Tian Q, Lu Y, Yan B, Wu C. Integrative Bioinformatics Analysis Reveals That miR-524-5p/MEF2C Regulates Bone Metastasis in Prostate Cancer and Breast Cancer. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:5211329. [PMID: 36128051 PMCID: PMC9482681 DOI: 10.1155/2022/5211329] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/28/2022] [Indexed: 11/30/2022]
Abstract
Bone metastases are highly prevalent in patients with advanced prostate cancer and breast cancer and have a serious impact on the survival time and quality of life of these patients. It has been reported that microRNAs (miRNAs) are expressed abnormally in different types of cancer and metastases. However, it remains unknown whether the underlying miRNAs are associated with prostate and breast cancer bone metastasis. Differentially expressed miRNAs (DE-miRNAs) and their potential targets in the metastatic process were identified by bioinformatics analysis. Additionally, qPCR confirmed that the miR-524-5p expression was downregulated in prostate and breast cancer cells. The overexpression of miR-524-5p restrained cell proliferation, invasion, and metastasis in prostate and breast cancer cells. Meanwhile, miR-524-5p could target and inhibit the expression of MEF2C, which was verified by a luciferase assay. In conclusion, our data strongly suggest that downregulation of miR-524-5p appears to be a precocious event in prostate and breast cancer, and the miR-524-5p/MEF2C axis plays a novel role in bone metastases from prostate and breast cancers.
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Affiliation(s)
- QingHua Tian
- Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - YingYing Lu
- Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - BiCong Yan
- Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - ChunGen Wu
- Department of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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31
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Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis. BLOOD SCIENCE 2022; 4:125-132. [DOI: 10.1097/bs9.0000000000000123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/31/2022] [Indexed: 11/25/2022] Open
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Stieg DC, Wang Y, Liu LZ, Jiang BH. ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance. Int J Mol Sci 2022; 23:ijms23126702. [PMID: 35743145 PMCID: PMC9223852 DOI: 10.3390/ijms23126702] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/05/2022] [Accepted: 06/14/2022] [Indexed: 12/11/2022] Open
Abstract
The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are involved in regulating OC angiogenesis through mediating multiple angiogenic factors such as hypoxia-induced factor (HIF-1) and vascular endothelial growth factor (VEGF). The NAPDH oxidase subunit NOX4 plays an important role in inducing endogenous ROS production in OC. This review will discuss several important miRNAs, NOX4, and ROS, which contribute to therapeutic resistance in OC, highlighting the effective therapeutic potential of OC through these mechanisms.
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Affiliation(s)
- David C. Stieg
- Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA; (D.C.S.); (L.-Z.L.)
| | - Yifang Wang
- Department of Pathology, Anatomy & Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA;
| | - Ling-Zhi Liu
- Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA; (D.C.S.); (L.-Z.L.)
| | - Bing-Hua Jiang
- Department of Pathology, Anatomy & Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA;
- Correspondence:
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MicroRNA Regulation of Human Herpesvirus Latency. Viruses 2022; 14:v14061215. [PMID: 35746686 PMCID: PMC9231095 DOI: 10.3390/v14061215] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 05/29/2022] [Accepted: 05/30/2022] [Indexed: 12/04/2022] Open
Abstract
Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate from it. Latent infection entails suppression of viral replication, maintenance of the viral genome in infected cells, and the ability to reactivate. Most human herpesviruses encode microRNAs (miRNAs) that regulate these processes during latency. Meanwhile, cellular miRNAs are hijacked by herpesviruses to participate in these processes. The viral or cellular miRNAs either directly target viral transcripts or indirectly affect viral infection through host pathways. These findings shed light on the molecular determinants that control the lytic-latent switch and may lead to novel therapeutics targeting latent infection. We discuss the multiple mechanisms by which miRNAs regulate herpesvirus latency, focusing on the patterns in these mechanisms.
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Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Alshaer W, Hasan H, Albakri KA, Alkhafaji E, Issa NN, Al-Holy MA, Abderrahman SM, Abdallah AM, Mohamud R. Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects. Biomedicines 2022; 10:1219. [PMID: 35740242 PMCID: PMC9219990 DOI: 10.3390/biomedicines10061219] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023] Open
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant's early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
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Affiliation(s)
- Ma’mon M. Hatmal
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Mohammad A. I. Al-Hatamleh
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| | - Amin N. Olaimat
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Walhan Alshaer
- Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan;
| | - Hanan Hasan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan;
| | - Khaled A. Albakri
- Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Enas Alkhafaji
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan;
| | - Nada N. Issa
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Murad A. Al-Holy
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Salim M. Abderrahman
- Department of Biology and Biotechnology, Faculty of Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Atiyeh M. Abdallah
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
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Abstract
MicroRNAs (miRNAs) are key players in gene regulation that target specific mRNAs for degradation or translational repression. Each miRNA is synthesized as a miRNA duplex comprising two strands (5p and 3p). However, only one of the two strands becomes active and is selectively incorporated into the RNA-induced silencing complex in a process known as miRNA strand selection. Recently, significant progress has been made in understanding the factors and processes involved in strand selection. Here, we explore the selection and functionality of the miRNA star strand (either 5p or 3p), which is generally present in the cell at low levels compared to its partner strand and, historically, has been thought to possess no biological activity. We also highlight the concepts of miRNA arm switching and miRNA isomerism. Finally, we offer insights into the impact of aberrant strand selection on immunity and cancer. Leading us through this journey is miR-155, a well-established regulator of immunity and cancer, and the increasing evidence that its 3p strand plays a role in these arenas. Interestingly, the miR-155-5p/-3p ratio appears to vary dependent on the timing of the immune response, and the 3p strand seems to play a regulatory role upon its partner 5p strand.
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Affiliation(s)
- Owen Dawson
- School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
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36
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Gleba JJ, Kłopotowska D, Banach J, Mielko KA, Turlej E, Maciejewska M, Kutner A, Wietrzyk J. Micro-RNAs in Response to Active Forms of Vitamin D3 in Human Leukemia and Lymphoma Cells. Int J Mol Sci 2022; 23:ijms23095019. [PMID: 35563410 PMCID: PMC9104187 DOI: 10.3390/ijms23095019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/19/2022] [Accepted: 04/29/2022] [Indexed: 11/16/2022] Open
Abstract
Non-coding micro-RNA (miRNAs) regulate the protein expression responsible for cell growth and proliferation. miRNAs also play a role in a cancer cells’ response to drug treatment. Knowing that leukemia and lymphoma cells show different responses to active forms of vitamin D3, we decided to investigate the role of selected miRNA molecules and regulated proteins, analyzing if there is a correlation between the selected miRNAs and regulated proteins in response to two active forms of vitamin D3, calcitriol and tacalcitol. A total of nine human cell lines were analyzed: five leukemias: MV-4-1, Thp-1, HL-60, K562, and KG-1; and four lymphomas: Raji, Daudi, Jurkat, and U2932. We selected five miRNA molecules—miR-27b, miR-32, miR-125b, miR-181a, and miR-181b—and the proteins regulated by these molecules, namely, CYP24A1, Bak1, Bim, p21, p27, p53, and NF-kB. The results showed that the level of selected miRNAs correlates with the level of proteins, especially p27, Bak1, NFκB, and CYP24A1, and miR-27b and miR-125b could be responsible for the anticancer activity of active forms of vitamin D3 in human leukemia and lymphoma.
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Affiliation(s)
- Justyna Joanna Gleba
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
- Correspondence: ; Tel.: +48-1-904-207-2571
| | - Dagmara Kłopotowska
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
| | - Joanna Banach
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
| | - Karolina Anna Mielko
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Norwida 4/6, 50-373 Wroclaw, Poland
| | - Eliza Turlej
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
- Department of Experimental Biology, The Wroclaw University of Environmental and Life Sciences, Norwida 27 B, 50-375 Wroclaw, Poland
| | - Magdalena Maciejewska
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
| | - Andrzej Kutner
- Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha, 02-097 Warsaw, Poland;
| | - Joanna Wietrzyk
- Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; (D.K.); (J.B.); (K.A.M.); (E.T.); (M.M.); (J.W.)
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Jiang J, Lyu W, Chen N. A bibliometric analysis of diffuse large B-cell lymphoma research from 2001 to 2020. Comput Biol Med 2022; 146:105565. [PMID: 35594683 DOI: 10.1016/j.compbiomed.2022.105565] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 04/07/2022] [Accepted: 04/25/2022] [Indexed: 11/25/2022]
Abstract
Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma (NHL) with the highest incidence, accounting for approximately one-third of NHL cases. Given the accumulated scientific publications related to the DLBCL domain, this study aimed to provide a comprehensive review of DLBCL studies from this millennium using the bibliometric method. With a strict retrieval strategy applied in the Web of Science database, a total of 10,869 publications from 2001 to 2020 were obtained and exported. The temporal and geographical distribution of these publications and the performance of contributing countries, institutions, journals, and authors corresponding to these documents were investigated, as well as an in-depth content analysis through keyword co-occurrence. With regard to the most productive countries, the United States ranks first with 2344 (21.6%) publications and shows the most frequent collaborations with other countries. By contrast, China has demonstrated remarkable performance in the growth rate of publications over the years, and it ranks first in the number of publications in the last five years. The University of Texas System is the institution with the highest number of published articles (4.99%). Leukemia Lymphoma is the journal with the highest number of publications in this field which contributed 588 articles. Solid and close collaborations between scholars are becoming more frequent over the four five-year periods. Overall, the highest cooperation frequency in the last two decades happens to Gascoyne RD at the British Columbia Cancer Agency and British Columbia Cancer Research Center in Canada. By comparing the article citation and keyword co-occurrence in each five-year period, as well as the changes in keyword clusters over two decades, we conclude that the stage, evaluation, prognosis, and treatment of DLBCL have always been the research hotspots in this field. Meanwhile, the evolution of keyword co-occurrence over the years demonstrates that new clusters appear. For instance, the effect of ferroptosis mechanism in DLBCL, immunotherapy for DLBCL, and PDL-1, PDL-2, and CAR-T therapy have drawn increasing attention from academia. Our research highlights the key characteristics of DLBCL research and provides comprehensive insights into the research status and evolutions in this field.
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Affiliation(s)
- Junyi Jiang
- Center for Science Communication and Achievement Transformation, National Natural Science Foundation of China, 100085, Beijing, China
| | - Wei Lyu
- School of Business Administration, Northeastern University, 110169, Shenyang, Liaoning, China
| | - Na Chen
- Department of Hematology, Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China; Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 250021, Jinan, Shandong, China.
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38
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Jiang Y, Zhao L, Wu Y, Deng S, Cao P, Lei X, Yang X. The Role of NcRNAs to Regulate Immune Checkpoints in Cancer. Front Immunol 2022; 13:853480. [PMID: 35464451 PMCID: PMC9019622 DOI: 10.3389/fimmu.2022.853480] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/07/2022] [Indexed: 01/07/2023] Open
Abstract
At present, the incidence of cancer is becoming more and more common, but its treatment has always been a problem. Although a small number of cancers can be treated, the recurrence rates are generally high and cannot be completely cured. At present, conventional cancer therapies mainly include chemotherapy and radiotherapy, which are the first-line therapies for most cancer patients, but there are palliatives. Approaches to cancer treatment are not as fast as cancer development. The current cancer treatments have not been effective in stopping the development of cancer, and cancer treatment needs to be imported into new strategies. Non-coding RNAs (ncRNAs) is a hot research topic at present. NcRNAs, which include microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), participate in all aspects of cancer biology. They are involved in the progression of tumors into a new form, including B-cell lymphoma, glioma, or the parenchymal tumors such as gastric cancer and colon cancer, among others. NcRNAs target various immune checkpoints to affect tumor proliferation, differentiation, and development. This might represent a new strategy for cancer treatment.
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Affiliation(s)
- Yicun Jiang
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China
| | - Leilei Zhao
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China
| | - Yiwen Wu
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China
| | - Sijun Deng
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China
| | - Pu Cao
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China
| | - Xiaoyong Lei
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China.,Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Xiaoyan Yang
- School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, China.,Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, China
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Malik S, Kumar V, Liu CH, Shih KC, Krueger S, Nieh MP, Bahal R. Head on Comparison of Self- and Nano-assemblies of Gamma Peptide Nucleic Acid Amphiphiles. ADVANCED FUNCTIONAL MATERIALS 2022; 32:2109552. [PMID: 35210986 PMCID: PMC8863176 DOI: 10.1002/adfm.202109552] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Indexed: 05/14/2023]
Abstract
Peptide nucleic acids (PNAs) are nucleic acid analogs with superior hybridization properties and enzymatic stability than deoxyribonucleic acid (DNA). In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymer due to the Watson-Crick -based molecular recognition and flexibility of synthesis. Here, we engineered PNA amphiphiles using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γPNA) amphiphiles self-assemble into spherical vesicles. Further, we formulate nano-assemblies using the amphiphilic γPNA as a polymer via ethanol injection-based protocols. We perform comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and nano-assemblies. Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) analysis reveal ellipsoidal morphology of γPNA nano-assemblies that results in superior cellular delivery compate to the spherical self-assembly. Next, we compare the functional activities of γPNA self-and nano-assemblies in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays. Overall, we establish that γPNA amphiphile is a functionally active bio-polymer to formulate nano-assemblies for a wide range of biomedical applications.
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Affiliation(s)
- Shipra Malik
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA
| | - Vikas Kumar
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA
| | - Chung-Hao Liu
- Polymer Program, Institute of Material Sciences, University of Connecticut, 191 Auditorium Road, Storrs, CT, 06269, USA
| | - Kuo-Chih Shih
- Polymer Program, Institute of Material Sciences, University of Connecticut, 191 Auditorium Road, Storrs, CT, 06269, USA
| | - Susan Krueger
- National Institute of Standards and Technology, Gaithersburg, MD 20899-6102, USA
| | - Mu-Ping Nieh
- Polymer Program, Institute of Material Sciences, University of Connecticut, 191 Auditorium Road, Storrs, CT, 06269, USA
| | - Raman Bahal
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA
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40
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Song G, Ma Y, Ma Y, Liu P, Hou L, Xu Z, Jiang J, Shen Y, Cao Y, Zhao Y. MiR-335-5p Targets SDC1 to Regulate Progression of Breast Cancer. Crit Rev Eukaryot Gene Expr 2022; 32:21-31. [DOI: 10.1615/critreveukaryotgeneexpr.2022041813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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41
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Shui B, La Rocca G, Ventura A, Haigis KM. Interplay between K-RAS and miRNAs. Trends Cancer 2022; 8:384-396. [PMID: 35093302 PMCID: PMC9035052 DOI: 10.1016/j.trecan.2022.01.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/25/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023]
Abstract
K-RAS is frequently mutated in cancers, and its overactivation can lead to oncogene-induced senescence (OIS), a barrier to cellular transformation. Feedback onto K-RAS limits its signaling to avoid senescence while achieving the appropriate level of activation that promotes proliferation and survival. Such regulation could be mediated by miRNAs, as aberrant RAS signaling and miRNA activity coexist in several cancers, with miRNAs acting both up- and downstream of K-RAS. Several miRNAs both regulate and are regulated by K-RAS, suggesting a noncoding RNA-based feedback mechanism. Functional interactions between K-RAS and the miRNA machinery have also begun to unfold. This review comprehensively surveys the state of knowledge connecting K-RAS to miRNA function and proposes a model for the regulation of K-RAS signaling by noncoding RNAs.
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Sajjadi-Dokht M, Merza Mohamad TA, Rahman HS, Maashi MS, Danshina S, Shomali N, Solali S, Marofi F, Zeinalzadeh E, Akbari M, Adili A, Aslaminabad R, Hagh MF, Jarahian M. MicroRNAs and JAK/STAT3 signaling: A new promising therapeutic axis in blood cancers. Genes Dis 2021; 9:849-867. [PMID: 35685482 PMCID: PMC9170603 DOI: 10.1016/j.gendis.2021.10.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 09/16/2021] [Accepted: 10/22/2021] [Indexed: 11/27/2022] Open
Abstract
Blood disorders include a wide spectrum of blood-associated malignancies resulting from inherited or acquired defects. The ineffectiveness of existing therapies against blood disorders arises from different reasons, one of which is drug resistance, so different types of leukemia may show different responses to treatment. Leukemia occurs for a variety of genetic and acquired reasons, leading to uncontrolled proliferation in one or more cell lines. Regarding the genetic defects, oncogene signal transducer and activator of transcription (STAT) family transcription factor, especially STAT3, play an essential role in hematological disorders onset and progress upon mutations, dysfunction, or hyperactivity. Besides, microRNAs, as biological molecules, has been shown to play a dual role in either tumorigenesis and tumor suppression in various cancers. Besides, a strong association between STAT3 and miRNA has been reported. For example, miRNAs can regulate STAT3 via targeting its upstream mediators such as IL6, IL9, and JAKs or directly binding to the STAT3 gene. On the other hand, STAT3 can regulate miRNAs. In this review study, we aimed to determine the role of either microRNAs and STAT3 along with their effect on one another's activity and function in hematological malignancies.
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43
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Bartlett B, Gao Z, Schukking M, Menor M, Khadka VS, Fabbri M, Fei P, Deng Y. The miRNA Profile of Inflammatory Colorectal Tumors Identify TGF-β as a Companion Target for Checkpoint Blockade Immunotherapy. Front Cell Dev Biol 2021; 9:754507. [PMID: 34722540 PMCID: PMC8551827 DOI: 10.3389/fcell.2021.754507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/13/2021] [Indexed: 12/21/2022] Open
Abstract
Extrinsic factors such as expression of PD-L1 (programmed dealth-ligand 1) in the tumor microenvironment (TME) have been shown to correlate with responses to checkpoint blockade therapy. More recently two intrinsic factors related to tumor genetics, microsatellite instability (MSI), and tumor mutation burden (TMB), have been linked to high response rates to checkpoint blockade drugs. These response rates led to the first tissue-agnostic approval of any cancer therapy by the FDA for the treatment of metastatic, MSI-H tumors with anti-PD-1 immunotherapy. But there are still very few studies focusing on the association of miRNAs with immune therapy through checkpoint inhibitors. Our team sought to explore the biology of such tumors further and suggest potential companion therapeutics to current checkpoint inhibitors. Analysis by Pearson Correlation revealed 41 total miRNAs correlated with mutation burden, 62 miRNAs correlated with MSI, and 17 miRNAs correlated with PD-L1 expression. Three miRNAs were correlated with all three of these tumor features as well as M1 macrophage polarization. No miRNAs in any group were associated with overall survival. TGF-β was predicted to be influenced by these three miRNAs (p = 0.008). Exploring miRNA targets as companions to treatment by immune checkpoint blockade revealed three potential miRNA targets predicted to impact TGF-β. M1 macrophage polarization state was also associated with tumors predicted to respond to therapy by immune checkpoint blockade.
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Affiliation(s)
- Bjarne Bartlett
- Bioinformatics Core, Department of Quantitative Health Sciences, University of Hawaii, Honolulu, HI, United States.,Department of Molecular Biosciences and Bioengineering, University of Hawai'i at Mānoa, Honolulu, HI, United States
| | - Zitong Gao
- Bioinformatics Core, Department of Quantitative Health Sciences, University of Hawaii, Honolulu, HI, United States.,Department of Molecular Biosciences and Bioengineering, University of Hawai'i at Mānoa, Honolulu, HI, United States
| | - Monique Schukking
- Department of Molecular Biosciences and Bioengineering, University of Hawai'i at Mānoa, Honolulu, HI, United States.,Cancer Biology Program, University of Hawai'i Cancer Center, Honolulu, HI, United States
| | - Mark Menor
- Bioinformatics Core, Department of Quantitative Health Sciences, University of Hawaii, Honolulu, HI, United States
| | - Vedbar S Khadka
- Bioinformatics Core, Department of Quantitative Health Sciences, University of Hawaii, Honolulu, HI, United States
| | - Muller Fabbri
- Cancer Biology Program, University of Hawai'i Cancer Center, Honolulu, HI, United States
| | - Peiwen Fei
- Cancer Biology Program, University of Hawai'i Cancer Center, Honolulu, HI, United States
| | - Youping Deng
- Bioinformatics Core, Department of Quantitative Health Sciences, University of Hawaii, Honolulu, HI, United States.,Department of Molecular Biosciences and Bioengineering, University of Hawai'i at Mānoa, Honolulu, HI, United States
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44
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Sempere LF, Azmi AS, Moore A. microRNA-based diagnostic and therapeutic applications in cancer medicine. WILEY INTERDISCIPLINARY REVIEWS. RNA 2021; 12:e1662. [PMID: 33998154 PMCID: PMC8519065 DOI: 10.1002/wrna.1662] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 04/10/2021] [Accepted: 04/12/2021] [Indexed: 01/18/2023]
Abstract
It has been almost two decades since the first link between microRNAs and cancer was established. In the ensuing years, this abundant class of short noncoding regulatory RNAs has been studied in virtually all cancer types. This tremendously large body of research has generated innovative technological advances for detection of microRNAs in tissue and bodily fluids, identified the diagnostic, prognostic, and/or predictive value of individual microRNAs or microRNA signatures as potential biomarkers for patient management, shed light on regulatory mechanisms of RNA-RNA interactions that modulate gene expression, uncovered cell-autonomous and cell-to-cell communication roles of specific microRNAs, and developed a battery of viral and nonviral delivery approaches for therapeutic intervention. Despite these intense and prolific research efforts in preclinical and clinical settings, there are a limited number of microRNA-based applications that have been incorporated into clinical practice. We review recent literature and ongoing clinical trials that highlight most promising approaches and standing challenges to translate these findings into viable microRNA-based clinical tools for cancer medicine. This article is categorized under: RNA in Disease and Development > RNA in Disease.
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Affiliation(s)
- Lorenzo F. Sempere
- Department of Radiology, Precision Health ProgramMichigan State UniversityEast LansingMichiganUSA
| | - Asfar S. Azmi
- Department of OncologyWayne State University School of MedicineDetroitMichiganUSA
- Karmanos Cancer InstituteDetroitMichiganUSA
| | - Anna Moore
- Departments of Radiology and Physiology, Precision Health ProgramMichigan State UniversityEast LansingMichiganUSA
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Alsaadi M, Khan MY, Dalhat MH, Bahashwan S, Khan MU, Albar A, Almehdar H, Qadri I. Dysregulation of miRNAs in DLBCL: Causative Factor for Pathogenesis, Diagnosis and Prognosis. Diagnostics (Basel) 2021; 11:1739. [PMID: 34679437 PMCID: PMC8535125 DOI: 10.3390/diagnostics11101739] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 11/16/2022] Open
Abstract
MicroRNA is a small non-coding RNA (sncRNA) involved in gene silencing and regulating post-transcriptional gene expression. miRNAs play an essential role in the pathogenesis of numerous diseases, including diabetes, cardiovascular diseases, viral diseases and cancer. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma (NHL), arising from different stages of B-cell differentiation whose pathogenesis involves miRNAs. Various viral and non-viral vectors are used as a delivery vehicle for introducing specific miRNA inside the cell. Adenoviruses are linear, double-stranded DNA viruses with 35 kb genome size and are extensively used in gene therapy. Meanwhile, Adeno-associated viruses accommodate up to 4.8 kb foreign genetic material and are favorable for transferring miRNA due to small size of miRNA. The genetic material is integrated into the DNA of the host cell by retroviruses so that only dividing cells are infected and stable expression of miRNA is achieved. Over the years, remarkable progress was made to understand DLBCL biology using advanced genomics and epigenomics technologies enabling oncologists to uncover multiple genetic mutations in DLBCL patients. These genetic mutations are involved in epigenetic modification, ability to escape immunosurveillance, impaired BCL6 and NF-κβ signaling pathways and blocking terminal differentiation. These pathways have since been identified and used as therapeutic targets for the treatment of DLBCL. Recently miRNAs were also identified to act either as oncogenes or tumor suppressors in DLBCL pathology by altering the expression levels of some of the known DLBCL related oncogenes. i.e., miR-155, miR-17-92 and miR-21 act as oncogenes by altering the expression levels of MYC, SHIP and FOXO1, respectively, conversely; miR-34a, mir-144 and miR-181a act as tumor suppressors by altering the expression levels of SIRT1, BCL6 and CARD11, respectively. Hundreds of miRNAs have already been identified as biomarkers in the prognosis and diagnosis of DLBCL because of their significant roles in DLBCL pathogenesis. In conclusion, miRNAs in addition to their role as biomarkers of prognosis and diagnosis could also serve as potential therapeutic targets for treating DLBCL.
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Affiliation(s)
- Mohammed Alsaadi
- Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia; (M.A.); (M.Y.K.); (A.A.); (H.A.)
- Hematology Research Unit, King Fahad Medical Research Center, King AbdulAziz University, Jeddah 21589, Saudi Arabia;
| | - Muhammad Yasir Khan
- Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia; (M.A.); (M.Y.K.); (A.A.); (H.A.)
- Vaccine and Immunotherapy Unit, King Fahad Medical Research Center, King AbdulAziz University, Jeddah 21589, Saudi Arabia
| | - Mahmood Hassan Dalhat
- Department of Biochemistry, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia;
| | - Salem Bahashwan
- Hematology Research Unit, King Fahad Medical Research Center, King AbdulAziz University, Jeddah 21589, Saudi Arabia;
- Department of Hematology, Faculty of Medicine, King AbdulAziz University, Jeddah 21589, Saudi Arabia
- King AbdulAziz University Hospital, King AbdulAziz University, Jeddah 21589, Saudi Arabia
| | - Muhammad Uzair Khan
- Department of Health Sciences, City University of Science and Information Technology, Peshawar 25000, Pakistan;
| | - Abdulgader Albar
- Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia; (M.A.); (M.Y.K.); (A.A.); (H.A.)
- Department of Microbiology, Faculty of Medicine, Jeddah University, Jeddah 23218, Saudi Arabia
| | - Hussein Almehdar
- Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia; (M.A.); (M.Y.K.); (A.A.); (H.A.)
| | - Ishtiaq Qadri
- Department of Biological Science, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia; (M.A.); (M.Y.K.); (A.A.); (H.A.)
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46
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Deng L, Ma Y, Ma P, Wu Y, Yang X, Deng Q. Toxic effect of cooking oil fume (COF) on lungs: Evidence of endoplasmic reticulum stress in rat. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2021; 221:112463. [PMID: 34198188 DOI: 10.1016/j.ecoenv.2021.112463] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/07/2021] [Accepted: 06/23/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Cooking oil fumes (COF) is one of the primary sources of indoor air pollution in China, which is associated with respiratory diseases such as acute lung injury and lung cancer. However, evidence of COF toxic effect was few. OBJECTIVES The research was aimed to investigate the toxic effect and the underlying mechanisms induced by COF. METHODS The female Wistar rats were randomly divided into several groups, including control group, COF exposure group and VE protection group, and instilled intratracheally with different COF suspensions (0.2, 2, 20 mg/kg) or saline once every 3 days for 30 days. After 24 h of final exposure, all rat were anesthetic euthanasia to draw materials. The alveolar lavage fluid (BALF) was for inflammatory cell count. The lung homogenate was to determine the biochemical indexes such as oxidative stress, apoptosis factors, carcinogenic toxicity and endoplasmic reticulum (ER) stress. The left lung was made for immunohistochemical and histopathological analysis. RESULTS The results showed that the levels of oxidative stress (ROS), apoptosis factors (NF-κB), carcinogenic toxicity (P53 and 8-OhdG), ER stress (IRE-1α and Caspase-12) in 2 mg/kg and 20 mg/kg COF exposure groups were significantly increased compared with the saline groups. The above pathological changes were improved after vitamin E (VE) supplementation. In addition, the immunohistochemical and histopathological analysis found the same trend. CONCLUSION The COF had health risk of heredity and potential carcinogenicity. Besides, COFs can not only induce oxidative stress, but also induce ER stress in lung and airway epithelial cells of female rats through the unfolded protein reaction (UPR) pathway. It revealed that the oxidative stress and ER stress interacted in aggravating lung injury. VE could effectively alleviate the lung injury causing by COF exposure.
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Affiliation(s)
- Linjing Deng
- school of tourism and ubran management, Jiangxi University of Finance and Economics, Nanchang 330000, China.
| | | | - Ping Ma
- School of Public Health, Hubei University of Science and Technology, Xianning 437100, China
| | - Yang Wu
- School of Public Health, Hubei University of Science and Technology, Xianning 437100, China
| | - Xu Yang
- Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University, Wuhan 430070, China
| | - Qihong Deng
- School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
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47
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Borum RM, Moore C, Chan SK, Steinmetz NF, Jokerst JV. A Photoacoustic Contrast Agent for miR-21 via NIR Fluorescent Hybridization Chain Reaction. Bioconjug Chem 2021; 33:1080-1092. [PMID: 34406744 DOI: 10.1021/acs.bioconjchem.1c00375] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Nucleic acids are well-established biomarkers of cancer with immense value in diagnostics and basic research. However, strategies to monitor these species in tissue can be challenging due to the need for amplification of imaging signal from low analyte concentrations with high specificity. Photoacoustic (PA) imaging is gaining traction for molecular imaging of proteins, small biomolecules, and nucleic acids by coupling pulsed near-infrared (NIR) excitation with broadband acoustic detection. This work introduces a PA nucleic acid contrast agent that harnesses NIR fluorophore and quencher-tagged hybridization chain reaction (HCR) for signal amplification. This HCR probe was designed to enable contact quenching between NIR dye-quencher pairs by coercing their direct alignment when miR-21, a microRNA cancer biomarker, is detected. The probe demonstrated a ratiometric PA limit of detection of 148 pM miR-21, sequence specificity against one- and two-base mutations, and selectivity over other microRNAs. It was further tested in live human ovarian cancer (SKOV3) and noncancerous (HEK 293T) cells to exemplify in situ PA activation based on differences in endogenous miR-21 regulation (p = 0.0002). The probe was lastly tested in tissue mimicking phantoms to exemplify sustained contrast in centimeter-range depths and 85.3% photostability after 15 min of laser irradiation. The probe's miR-21-specific activation and its ability to maintain contrast in biologically relevant absorbing and scattering media support its consideration for live-cell PA microscopy and potential cancer diagnostics. Results from this probe also underscore the combined detection power between ratiometric PA signaling and strand amplification for more sensitive DNA-based PA sensors.
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Affiliation(s)
- Raina M Borum
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093. United States
| | - Colman Moore
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093. United States
| | - Soo Khim Chan
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093. United States
| | - Nicole F Steinmetz
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093. United States.,Department of Radiology, University of California, San Diego, La Jolla, California 92093. United States.,Department of Bioengineering, University of California, San Diego, La Jolla, California 92093. United States.,Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, California 92093. United States.,Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, California 92093. United States.,Moores Cancer Center, University of California, San Diego, La Jolla, California 92037. United States
| | - Jesse V Jokerst
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093. United States.,Materials Science and Engineering Program, University of California, San Diego, La Jolla, California 92093. United States.,Department of Radiology, University of California, San Diego, La Jolla, California 92093. United States
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48
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Augenlicht A, Saiselet M, Decaussin-Petrucci M, Andry G, Dumont JE, Maenhaut C. MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways. Oncotarget 2021; 12:1587-1599. [PMID: 34381564 PMCID: PMC8351599 DOI: 10.18632/oncotarget.28030] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 07/13/2021] [Indexed: 12/14/2022] Open
Abstract
The aberrant expression of miRNAs is often correlated to tumor development. MiR-7-5p is a recently discovered downregulated miRNA in thyroid papillary carcinoma (PTC). The goal of this project was to characterize its functional role in thyroid tumorigenesis and to identify the targeted modulated pathways. MiR-7-5p overexpression following transfection in TPC1 and HT-ori3 cells decreased proliferation of the two thyroid cell lines. Analysis of global transcriptome modifications showed that miR-7-5p inhibits thyroid cell proliferation by modulating the MAPK and PI3K signaling pathways which are both necessary for normal thyroid proliferation and play central roles in PTC tumorigenesis. Several effectors of these pathways are indeed targets of miR-7-5p, among which EGFR and IRS2, two upstream activators. We confirmed the upregulation of IRS2 and EGFR in human PTC and showed the existence of a negative correlation between the decreased expression of miR-7-5p and the increased expression of IRS2 or EGFR. Our results thus support a tumor-suppressor activity of miR-7-5p. The decreased expression of miR-7-5p during PTC tumorigenesis might give the cells a proliferative advantage and delivery of miR-7-5p may represent an innovative approach for therapy.
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Affiliation(s)
- Alice Augenlicht
- Institute of Interdisciplinary Research, Université libre de Bruxelles, Brussels, Belgium
| | - Manuel Saiselet
- Institute of Interdisciplinary Research, Université libre de Bruxelles, Brussels, Belgium
| | - Myriam Decaussin-Petrucci
- Service d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre Benite Cedex 69495, France
| | - Guy Andry
- Surgery Department, J. Bordet Institute, Brussels 1000, Belgium
| | - Jacques E Dumont
- Institute of Interdisciplinary Research, Université libre de Bruxelles, Brussels, Belgium
| | - Carine Maenhaut
- Institute of Interdisciplinary Research, Université libre de Bruxelles, Brussels, Belgium
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Ben Dhia O, Lasram MM, Harizi N, Doghri R, Charfi L, Souai N, Najjari A, Ouzari HI, Ben-Hadj-Khalifa S. Kefir milk alleviates benzene-induced immunotoxicity and hematotoxicity in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:42230-42242. [PMID: 33797720 DOI: 10.1007/s11356-021-13569-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 03/16/2021] [Indexed: 06/12/2023]
Abstract
The adverse health effects of benzene occupational and circumstance pollution exposure are an increasing concern. It leads to damage to various human tissues including bone marrow and ovarian tissues and many vital physiological processes. Previous studies showed that kefir is a rich probiotic, having protective effect, thanks to its antioxidant, anti-inflammatory, and immunomodulatory capacity. The purpose of this study was to evaluate the potential efficacy of kefir to remediate benzene toxicity in rat. Thirty-two female rats were randomly allocated and administered orally with benzene and/or kefir during a period of 21 consecutive days. At the end of the experiment, hematological and bone marrow cell changes were estimated. The animals exposed to benzene exhibited anemia and a significant decrease in the levels of white blood cell. Moreover, benzene led to the activation of gene expression of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), a myelotoxicity in bone marrow cells. Our data showed that kefir treatment alleviated benzene-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in the bone marrow. Furthermore, these physiological results were observed with animals showing high concentrations of lactic acid bacteria (LAB) determined from fecal samples, which are considered an indicator of kefir-associated microorganisms. Our study suggests that kefir is a potential nutritional supplement target to attenuate hematotoxicity induced by benzene.
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Affiliation(s)
- Olfa Ben Dhia
- Laboratory of Microorganisms and Actives Biomolecules, Department of Biology, Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia.
| | - Mohamed Montassar Lasram
- Laboratory of Neurophysiology, Cellular Physiopathology and Bioressources Valorization, University of Tunis El Manar, Tunis, Tunisia
| | - Nouha Harizi
- Laboratory of Microorganisms and Actives Biomolecules, Department of Biology, Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia
| | - Raoudha Doghri
- Laboratory of Anatomy and Pathological Cytology, Salah Azaiez Institute, University of Tunis El Manar, Tunis, Tunisia
| | - Lamia Charfi
- Laboratory of Anatomy and Pathological Cytology, Salah Azaiez Institute, University of Tunis El Manar, Tunis, Tunisia
| | - Nessrine Souai
- Laboratory of Microorganisms and Actives Biomolecules, Department of Biology, Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia
| | - Afef Najjari
- Laboratory of Microorganisms and Actives Biomolecules, Department of Biology, Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia
| | - Hadda-Imene Ouzari
- Laboratory of Microorganisms and Actives Biomolecules, Department of Biology, Faculty of Sciences, University of Tunis El Manar, Tunis, Tunisia
| | - Sonia Ben-Hadj-Khalifa
- Laboratory of Neurophysiology, Cellular Physiopathology and Bioressources Valorization, University of Tunis El Manar, Tunis, Tunisia
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50
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Mi QS, Wang J, Liu Q, Wu X, Zhou L. microRNA dynamic expression regulates invariant NKT cells. Cell Mol Life Sci 2021; 78:6003-6015. [PMID: 34236444 PMCID: PMC11073247 DOI: 10.1007/s00018-021-03895-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/23/2021] [Accepted: 06/29/2021] [Indexed: 02/06/2023]
Abstract
Invariant natural killer T cells (iNKT) are a prevalent population of innate-like T cells in mice, but quite rare in humans that are critical for regulation of the innate and adaptive immune responses during antimicrobial immunity, tumor rejection, and inflammatory diseases. Multiple transcription factors and signaling molecules that contribute to iNKT cell selection and functional differentiation have been identified. However, the full molecular network responsible for regulating and maintaining iNKT populations remains unclear. MicroRNAs (miRNAs) are an abundant class of evolutionarily conserved, small, non-coding RNAs that regulate gene expression post-transcriptionally. Previous reports uncovered the important roles of miRNAs in iNKT cell development and function using Dicer mutant mice. In this review, we discuss the emerging roles of individual miRNAs in iNKT cells reported by our group and other groups, including miR-150, miR-155, miR-181, let-7, miR-17 ~ 92 cluster, and miR-183-96-182 cluster. It is likely that iNKT cell development, differentiation, homeostasis, and functions are orchestrated through a multilayered network comprising interactions among master transcription factors, signaling molecules, and dynamically expressed miRNAs. We provide a comprehensive view of the molecular mechanisms underlying iNKT cell differentiation and function controlled by dynamically expressed miRNAs.
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Affiliation(s)
- Qing-Sheng Mi
- Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA.
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.
- Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA.
| | - Jie Wang
- Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA
| | - Queping Liu
- Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA
| | - Xiaojun Wu
- Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA
| | - Li Zhou
- Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA.
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.
- Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, MI, 48202, USA.
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