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Yang Y, Razak SRA, Ismail IS, Ma Y, Yunus MA. Molecular mechanisms of miR-192 in cancer: a biomarker and therapeutic target. Cancer Cell Int 2025; 25:94. [PMID: 40087755 PMCID: PMC11908092 DOI: 10.1186/s12935-025-03666-5] [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: 09/09/2024] [Accepted: 01/29/2025] [Indexed: 03/17/2025] Open
Abstract
Cancer remains a major global health challenge due to its rising prevalence and high mortality rates. The field of microRNAs (miRNAs) has made significant progress in the understanding of tumorigenesis and has broadened our knowledge of their targeting, especially in cancer therapy. miRNAs, a class of small non-coding RNAs, participate in post-transcriptional gene regulation by translational inhibition or mRNA degradation. Among these, microRNA-192 (miR-192) is located on human chromosome 11q13.1, and is highly correlated with the occurrence and development of various human cancers. Dysregulation of miR-192 has been extensively studied in various pathological processes, including tumorigenesis, making it a valuable biomarker for cancer diagnosis and prognosis. The functional role of miR-192 varies across cancer types, acting as either a tumor suppressor or as an oncogene through the modulation of multiple gene expressions and downstream signaling pathways. However, the roles of miR-192 in cancer appear inconsistent across types, with current research often focused on specific genes or pathways, limiting insight into its broader impact on cellular signaling networks. Therefore, this review aims to provide a comprehensive overview of miR-192 research. The paper reviews differences in miR-192 expression in cancer and systematically summarizes the role of miR-192 in cancers. The review further explores the complex roles of miR-192 in various pathological processes, emphasizing its regulatory pathways, interaction networks, and association with tumor progression. This review also illustrates the clinical application of miR-192 as a diagnostic and prognostic biomarker for non-invasive cancer detection, as it is consistently present in both serum and exosomes. A comprehensive summary and analysis of the relationship between miR-192 and various cancers may provide valuable insights, potentially guiding novel approaches in clinical diagnosis, therapeutic strategies, and foundational cancer research.
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Affiliation(s)
- Yang Yang
- Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, Malaysia
- School of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Siti Razila Abdul Razak
- Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, Malaysia
| | - Ida Shazrina Ismail
- Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, Malaysia
| | - Yanxia Ma
- School of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.
| | - Muhammad Amir Yunus
- Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, Malaysia.
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Gao R, Li Q, Qiu M, Xie S, Sun X, Huang T. Serum exosomal miR-192 serves as a potential detective biomarker for early pregnancy screening in sows. Anim Biosci 2023; 36:1336-1349. [PMID: 37170506 PMCID: PMC10472158 DOI: 10.5713/ab.22.0422] [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: 11/04/2022] [Revised: 01/05/2023] [Accepted: 04/19/2023] [Indexed: 05/13/2023] Open
Abstract
OBJECTIVE The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. METHODS The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). RESULTS A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC] = 0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. CONCLUSION Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.
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Affiliation(s)
- Ruonan Gao
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
| | - Qingchun Li
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
| | - Meiyu Qiu
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
- Institute of Biotechnology, Xinjiang Academy of Animal Science, Urumqi, 830000,
China
| | - Su Xie
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
- Key Laboratory of Animal Breeding and Reproduction of Minstry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070,
China
| | - Xiaomei Sun
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
| | - Tao Huang
- College of Animal Science and Technology, Shihezi University, 221 North Fourth Road, Shihezi 832000,
China
- Xinjiang Pig Breeding Engineering Technology Research Center, Xinjiang Tecon Husbandry S&T Co. Ltd, Changji, 831100,
China
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Cai X, Yin W, Tang C, Lu Y, He Y. Molecular mechanism of microRNAs regulating apoptosis in osteosarcoma. Mol Biol Rep 2022; 49:6945-6956. [PMID: 35474050 DOI: 10.1007/s11033-022-07344-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 03/08/2022] [Indexed: 11/28/2022]
Abstract
Osteosarcoma is a primary malignant bone tumor with no effective treatment. Apoptosis, one of the programmed cell death, is any pathological form of cell death mediated by intracellular processes. Under the pathological state, the de-regulated regulation of apoptosis can disrupt the balance between cell proliferation and death, causing osteosarcoma proliferation and metastasis. As carcinogenic or tumor suppressor factors, microRNAs (miRNAs) regulate apoptosis of osteosarcoma cells by regulating apoptosis-related genes and apoptosis-related signaling pathways, such as mitochondrial apoptosis pathway, death receptor pathway, and endoplasmic reticulum pathway. Meanwhile as these abnormal miRNAs can be stored and transported by exosomes, detecting exosomes can be seen an effective method to diagnose osteosarcoma in the early stage. This review provides the current knowledge of miRNAs and their target genes related to the apoptosis of osteosarcoma, summarizes abnormal expression and regulation of miRNAs and signaling pathways in osteosarcoma and prospects the detection of exosome as a method for early diagnosis of osteosarcoma.
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Affiliation(s)
- Xueyang Cai
- School of Clinical Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou Province, China
| | - Wei Yin
- School of Clinical Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou Province, China
| | - Chao Tang
- School of Clinical Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou Province, China
| | - Yubao Lu
- Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, Guangdong Province, China
| | - Yuqi He
- Trauma Surgery Department, Hannover Medical School (MHH), OE 6230 Carl-Neuberg-Straße 1, 30625, Hanover, Germany.
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Quaglio AEV, Santaella FJ, Rodrigues MAM, Sassaki LY, Di Stasi LC. MicroRNAs expression influence in ulcerative colitis and Crohn's disease: A pilot study for the identification of diagnostic biomarkers. World J Gastroenterol 2021; 27:7801-7812. [PMID: 34963743 PMCID: PMC8661377 DOI: 10.3748/wjg.v27.i45.7801] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/14/2021] [Accepted: 11/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) comprises two distinct diseases, Crohn's disease (CD) and ulcerative colitis (UC), both of which are chronic, relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology. The incidence and prevalence of IBD are continually increasing, indicating the need for further studies to investigate the genetic determinants of these diseases. Since microRNAs (miRNAs) regulate protein translation via complementary binding to mRNA, discovering differentially expressed miRNAs (DE) in UC or CD patients could be important for diagnostic biomarker identification, assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis. AIM To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA. METHODS A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University (Unesp). The diagnosis of UC or CD was based on clinical, endoscopic, radiologic, and histological criteria and confirmed by histopathological analysis at the time of selection. The TaqMan™ Array Human MicroRNA A+B Cards Set v3.0 (Applied Biosystems™) platform was used to analyze 754 miRNAs. Targets of DE-miRNAs were predicted using miRNA Data Integration Portal (mirDIP) and the miRNA Target Interaction database (MiRTarBase). All statistical analyses were conducted using GraphPad Prism software. Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests, respectively. RESULTS The results showed that of the 754 miRNAs that were initially evaluated, 643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC; the remaining 111 miRNAs were not considered to be expressed in these patients. The expression levels of 28 miRNAs were significantly different between the CD and UC patients (P ≤ 0.05); 13 miRNAs demonstrated a fold-change in expression level greater than 1. Five miRNAs with a downregulated expression were selected for enrichment analysis. The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers. CONCLUSION MiRNAs could be used to differentiate UC from CD, and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.
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Affiliation(s)
- Ana Elisa Valencise Quaglio
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, São Paulo State University (Unesp), Institute of Biosciences, Botucatu 18618-689, São Paulo, Brazil
| | - Felipe Jose Santaella
- Department of Pathology, Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu 18618-687, São Paulo, Brazil
| | | | - Ligia Yukie Sassaki
- Department of Internal Medicine, Botucatu Medical School, São Paulo State University (Unesp), Botucatu 18618-687, São Paulo, Brazil
| | - Luiz Claudio Di Stasi
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, São Paulo State University (Unesp), Institute of Biosciences, Botucatu 18618-689, São Paulo, Brazil
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MotieGhader H, Safavi E, Rezapour A, Amoodizaj FF, Iranifam RA. Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis. Sci Rep 2021; 11:21872. [PMID: 34750486 PMCID: PMC8576023 DOI: 10.1038/s41598-021-01410-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/28/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness. This illness is spurred on by a coronavirus known as SARS-associated coronavirus (SARS-CoV). SARS was first detected in Asia in late February 2003. The genome of this virus is very similar to the SARS-CoV-2. Therefore, the study of SARS-CoV disease and the identification of effective drugs to treat this disease can be new clues for the treatment of SARS-Cov-2. This study aimed to discover novel potential drugs for SARS-CoV disease in order to treating SARS-Cov-2 disease based on a novel systems biology approach. To this end, gene co-expression network analysis was applied. First, the gene co-expression network was reconstructed for 1441 genes, and then two gene modules were discovered as significant modules. Next, a list of miRNAs and transcription factors that target gene co-expression modules' genes were gathered from the valid databases, and two sub-networks formed of transcription factors and miRNAs were established. Afterward, the list of the drugs targeting obtained sub-networks' genes was retrieved from the DGIDb database, and two drug-gene and drug-TF interaction networks were reconstructed. Finally, after conducting different network analyses, we proposed five drugs, including FLUOROURACIL, CISPLATIN, SIROLIMUS, CYCLOPHOSPHAMIDE, and METHYLDOPA, as candidate drugs for SARS-CoV-2 coronavirus treatment. Moreover, ten miRNAs including miR-193b, miR-192, miR-215, miR-34a, miR-16, miR-16, miR-92a, miR-30a, miR-7, and miR-26b were found to be significant miRNAs in treating SARS-CoV-2 coronavirus.
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Affiliation(s)
- Habib MotieGhader
- Department of Basic Sciences, Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
- Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
| | - Esmaeil Safavi
- Department of Basic Sciences, Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
- Department of Basic Sciences, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Ali Rezapour
- Department of Animal Science, Faculty of Agriculture, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Fatemeh Firouzi Amoodizaj
- Department of Basic Sciences, Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Roya Asl Iranifam
- Department of Basic Sciences, Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
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Rozhin P, Charitidis C, Marchesan S. Self-Assembling Peptides and Carbon Nanomaterials Join Forces for Innovative Biomedical Applications. Molecules 2021; 26:4084. [PMID: 34279424 PMCID: PMC8271590 DOI: 10.3390/molecules26134084] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/30/2021] [Accepted: 07/02/2021] [Indexed: 02/07/2023] Open
Abstract
Self-assembling peptides and carbon nanomaterials have attracted great interest for their respective potential to bring innovation in the biomedical field. Combination of these two types of building blocks is not trivial in light of their very different physico-chemical properties, yet great progress has been made over the years at the interface between these two research areas. This concise review will analyze the latest developments at the forefront of research that combines self-assembling peptides with carbon nanostructures for biological use. Applications span from tissue regeneration, to biosensing and imaging, and bioelectronics.
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Affiliation(s)
- Petr Rozhin
- Chemical and Pharmaceutical Sciences Department, University of Trieste, 34127 Trieste, Italy;
| | - Costas Charitidis
- School of Chemical Engineering, National Technical University of Athens, Iroon Polytechneiou 9, Zografou, 157 80 Athens, Greece;
| | - Silvia Marchesan
- Chemical and Pharmaceutical Sciences Department, University of Trieste, 34127 Trieste, Italy;
- INSTM, Unit of Trieste, 34127 Trieste, Italy
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de Sá Pereira BM, Montalvão de Azevedo R, da Silva Guerra JV, Faria PA, Soares-Lima SC, De Camargo B, Maschietto M. Non-coding RNAs in Wilms' tumor: biological function, mechanism, and clinical implications. J Mol Med (Berl) 2021; 99:1043-1055. [PMID: 33950291 DOI: 10.1007/s00109-021-02075-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 03/04/2021] [Accepted: 04/06/2021] [Indexed: 10/21/2022]
Abstract
Non-coding RNAs are involved with maintenance and regulation of physiological mechanisms and are involved in pathological processes, such as cancer. Among the small ncRNAs, miRNAs are the most explored in tumorigenesis, metastasis development, and resistance to chemotherapy. These small molecules of ~ 22 nucleotides are modulated during early renal development, involved in the regulation of gene expression and Wilms' tumor progression. Wilms' tumors are embryonic tumors with few mutations and complex epigenetic dysregulation. In recent years, the small ncRNAs have been explored as potentially related both in physiological development and in the tumorigenesis of several types of cancer. Besides, genes regulated by miRNAs are related to biological pathways as PI3K, Wnt, TGF-β, and Hippo signaling pathways, among others, which may be involved with the underlying mechanisms of resistance to chemotherapy, and in this way, it has emerged as potential targets for cancer therapies, including for Wilms' tumors.
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Affiliation(s)
| | - Rafaela Montalvão de Azevedo
- Brazilian National Cancer Institute (INCa), Rio de Janeiro, RJ, Brazil.,Current institution: Molecular Bases of Genetic Risk and Genetic Testing Unit, Research Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - João Victor da Silva Guerra
- Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil.,Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmaceutic Sciences, University of Campinas, Campinas, SP, Brazil
| | - Paulo A Faria
- Brazilian National Cancer Institute (INCa), Rio de Janeiro, RJ, Brazil
| | | | | | - Mariana Maschietto
- Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil. .,Current: Research Institute, Boldrini Children's Hospital, Rua Dr. Gabriel Porto, 1270 - Cidade Universitária, Campinas, SP, 13083-210, Brazil.
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Diagnostic and Prognostic Role of miR-192 in Different Cancers: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8851035. [PMID: 33614788 PMCID: PMC7878092 DOI: 10.1155/2021/8851035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 12/17/2020] [Accepted: 01/15/2021] [Indexed: 12/18/2022]
Abstract
Introduction It has been shown that miR-192 is abnormally expressed in a variety of cancer types and participates in different kinds of signaling pathways. The role of miR-192 in the diagnosis and prognosis of cancer has not been verified. This article is aimed at exploring the diagnostic and prognostic value of miR-192 through a systematic review and meta-analysis. Methods A systematic search was performed through PubMed, Embase, Web of Science, and Cochrane Library databases up to June 16, 2020. A total of 16 studies were enrolled in the meta-analyses, of which 11 articles were used for diagnostic meta-analysis and 5 articles were used for prognostic meta-analysis. The values of sensitivity and specificity using miR-192 expression as a diagnostic tool were pooled in the diagnostic meta-analysis. The hazard ratios (HRs) of overall survival (OS) with 95 confidence intervals (CIs) were extracted from the studies, and pooled HRs were evaluated in the prognostic meta-analysis. Eleven studies including 667 cancer patients and 514 controls met the eligibility criteria for the diagnostic meta-analysis. Five studies including 166 patients with high miR-192 expression and 236 patients with low miR-192 expression met the eligibility criteria for the prognostic meta-analysis. Results The overall diagnostic accuracy was as follows: sensitivity 0.79 (95%CI = 0.75-0.82), specificity 0.74 (95%CI = 0.64-0.82), positive likelihood ratio 3.03 (95%CI = 2.11-4.34), negative likelihood ratio 0.29 (95%CI = 0.23-0.37), diagnostic odds ratio 10.50 (95%CI = 5.89-18.73), and area under the curve ratio (AUC) 0.82 (95%CI = 0.78-0.85). The overall prognostic analysis showed that high expression of miR-192 in patients was associated with positive survival (HR = 0.62, 95%CI : 0.41-0.93, p = 0.020). Conclusion Our results revealed that miR-192 was a potential biomarker with good sensitivity and specificity in cancers. Moreover, highly expressed miR-192 predicted a good prognosis for patients.
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Grzywa TM, Klicka K, Włodarski PK. Regulators at Every Step-How microRNAs Drive Tumor Cell Invasiveness and Metastasis. Cancers (Basel) 2020; 12:E3709. [PMID: 33321819 PMCID: PMC7763175 DOI: 10.3390/cancers12123709] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/03/2020] [Accepted: 12/07/2020] [Indexed: 02/06/2023] Open
Abstract
Tumor cell invasiveness and metastasis are the main causes of mortality in cancer. Tumor progression is composed of many steps, including primary tumor growth, local invasion, intravasation, survival in the circulation, pre-metastatic niche formation, and metastasis. All these steps are strictly controlled by microRNAs (miRNAs), small non-coding RNA that regulate gene expression at the post-transcriptional level. miRNAs can act as oncomiRs that promote tumor cell invasion and metastasis or as tumor suppressor miRNAs that inhibit tumor progression. These miRNAs regulate the actin cytoskeleton, the expression of extracellular matrix (ECM) receptors including integrins and ECM-remodeling enzymes comprising matrix metalloproteinases (MMPs), and regulate epithelial-mesenchymal transition (EMT), hence modulating cell migration and invasiveness. Moreover, miRNAs regulate angiogenesis, the formation of a pre-metastatic niche, and metastasis. Thus, miRNAs are biomarkers of metastases as well as promising targets of therapy. In this review, we comprehensively describe the role of various miRNAs in tumor cell migration, invasion, and metastasis.
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Affiliation(s)
- Tomasz M. Grzywa
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (T.M.G.); (K.K.)
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Klaudia Klicka
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (T.M.G.); (K.K.)
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Paweł K. Włodarski
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (T.M.G.); (K.K.)
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Chen Z, Wang X, Hou X, Ding F, Yi K, Zhang P, You T. Knockdown of Long Non-Coding RNA AFAP1-AS1 Promoted Viability and Suppressed Death of Cardiomyocytes in Response to I/R In Vitro and In Vivo. J Cardiovasc Transl Res 2020; 13:996-1007. [PMID: 32406007 DOI: 10.1007/s12265-020-10016-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 04/24/2020] [Indexed: 12/13/2022]
Abstract
Long non-coding RNA (lncRNA) plays a pivotal role in the development of myocardial infarction (MI). The aim of this study was to investigate the effects of lncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on cell cycle, proliferation, and apoptosis. RT-qPCR was used to detect the expression levels of AFAP1-AS1, miR-512-3p, and reticulon 3 (RTN3) in rat model of I/R. The simulated MI environment was constructed. MTT assay and flow cytometry were used to detect changes in cardiomyocyte viability and cell cycle/apoptosis after MI by AFAP1-AS1 silencing or RTN3 silencing. The targeting relationship of miR-512-3p and AFAP1-AS1 and RTN3 in cardiomyocytes was verified by dual luciferase reporter assay. The expression levels of AFAP1-AS1 and RTN3 were significantly upregulated in a rat model of LAD ligation (or MI) ligation, while the expression level of miR-512-3p was significantly reduced. Overexpressed AFAP1-AS1 and RTN3 promoted cardiomyocyte apoptosis and inhibited cardiomyocyte proliferation. MiR-512-3p was a direct target of AFAP1-AS1, and RTN3 was a direct target of miR-512-3p. AFAP1-AS1 promoted the progression of MI by targeting miR-512-3p. AFAP1-AS1 promoted the progression of MI by modulating the miR-512-3p/RTN3 axis. AFAP1-AS1 may be a potential therapy target for MI. Graphical Abstract The role of AFAP1-AS1 in regulating MI injury in vivo. (A) Effect of AFAP1-AS1 in MI injury in vivo. (B) The mRNA level of RTN3 in MI injury in vivo. (C) The protein level of RTN3 in MI injury in vivo. (D) Effect of miR-512-3p in MI model group. (E) TUNEL assay. *P < 0.05, **P < 0.01 vs the sham group; #P < 0.05, ##P < 0.01 vs the MI group.
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Affiliation(s)
- Zhigong Chen
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Department of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Xinkuan Wang
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Xiaodong Hou
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Fan Ding
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Kang Yi
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Peng Zhang
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China
| | - Tao You
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, No. 204, Dong gang West Road, Chengguan District, Lanzhou City, Gansu province, 730000, People's Republic of China.
- Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou, 730000, People's Republic of China.
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Li H, He L, Tuo Y, Huang Y, Qian B. Circular RNA hsa_circ_0000282 contributes to osteosarcoma cell proliferation by regulating miR-192/XIAP axis. BMC Cancer 2020; 20:1026. [PMID: 33097010 PMCID: PMC7583201 DOI: 10.1186/s12885-020-07515-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/09/2020] [Indexed: 01/20/2023] Open
Abstract
Background Circular RNAs (circRNAs) have emerged as a novel category of non-coding RNA, which exhibit a pivotal effect on regulating gene expression and biological functions, yet how circRNAs function in osteosarcoma (OSA) still demands further investigation. This study aimed at probing into the function of hsa_circ_0000282 in OSA. Methods The expressions of circ_0000282 and miR-192 in OSA tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of circ_0000282 and clinicopathological features of OSA patients was analyzed. The expressions of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in OSA cells were assayed by Western blot. The proliferation and apoptosis of OSA cells were examined by CCK-8, BrdU and flow cytometry, respectively. Bioinformatics analysis, dual-luciferase reporter gene assay and RIP experiments were employed to predict and validate the targeting relationships between circ_0000282 and miR-192, and between miR-192 and XIAP, respectively. Results Circ_0000282 was highly expressed in OSA tissues and cell lines, which represented positive correlation with Enneking stage of OSA patients and negative correlation with tumor differentiation degree. In vitro experiments confirmed that overexpression of circ_0000282 markedly facilitated OSA cell proliferation and repressed cancer cell apoptosis in comparison to control group. Besides, knockdown of circ_0000282 repressed OSA cell proliferation and promoted apoptosis. Additionally, the binding relationships between circ_0000282 and miR-192, and between miR-192 and XIAP were validated. Circ_0000282 indirectly up-regulated XIAP expression by adsorbing miR-192, thereby playing a role in promoting cancer in OSA. Conclusion Circ_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.
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Affiliation(s)
- Houkun Li
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 76 Nanguo Road, Xi'an, 710054, Shaanxi, China.
| | - Limin He
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 76 Nanguo Road, Xi'an, 710054, Shaanxi, China
| | - Yuan Tuo
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 76 Nanguo Road, Xi'an, 710054, Shaanxi, China
| | - Yansheng Huang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 76 Nanguo Road, Xi'an, 710054, Shaanxi, China
| | - Bing Qian
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 76 Nanguo Road, Xi'an, 710054, Shaanxi, China
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Sun S, Fu L, Wang G, Wang J, Xu L. MicroRNA-431-5p Inhibits the Tumorigenesis of Osteosarcoma Through Targeting PANX3. Cancer Manag Res 2020; 12:8159-8169. [PMID: 32982413 PMCID: PMC7490058 DOI: 10.2147/cmar.s260149] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 08/13/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose This study aimed to evaluate the regulatory role of miR-431-5p on the tumorigenesis of osteosarcoma (OS) and the underlying mechanism involving pannexin 3 (PANX3). Methods qRT-PCR was applied to measure the expression of miR-431-5p in OS tissues and cells. PANX3 and miR-431-5p were overexpressed in U2OS and HOS cells. The cell viability and apoptosis were determined by MTT and FITC/PI double staining assay, respectively. Transwell assay was performed to detect cell migration and invasion. The protein expression of cleave-caspase-3 and MMP-2/-9 was detected by Western blot. The target relationship between miR-431-5p and PANX3 was predicated by ENCORI and identified by DLR assay. The anti-tumor effect of miR-431-5p was further analyzed in a xenograft tumor model in mice. Results MiR-431-5p expression was down-regulated in OS tissues and negatively correlated with lymph node metastasis and TNM stage. Over-expression of miR-431-5p induced cell apoptosis, inhibited cell proliferation, migration and invasion, up-regulated cleave-caspase-3, and down-regulated MMP-2 and -9 in OS cells. Over-expression of miR-431-5p also inhibited the growth of tumor xenografts in mice. In addition, PANX3 was a target of miR-431-5p. Over-expression of PANX3 reversed the anti-tumor effect of miR-431-5p mimics on U2OS and HOS cells. Conclusion Up-regulation of miR-431-5p suppressed the tumorigenesis of OS via targeting PANX3.
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Affiliation(s)
- Shengliang Sun
- Department of Orthopedic Trauma, The 89th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong, People's Republic of China
| | - Lei Fu
- Department of Orthopedic Trauma, The 89th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong, People's Republic of China
| | - Gen Wang
- Department of Orthopedic Trauma, The 89th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong, People's Republic of China
| | - Jianli Wang
- Department of Orthopedic Trauma, The 89th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong, People's Republic of China
| | - Liping Xu
- Department of Oncology, The 89th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong, People's Republic of China
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13
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Luo X, Tang J, Xuan H, Liu J, Li X. Identification and Validation of a Potent Multi-miRNA Signature for Prediction of Prognosis of Osteosarcoma Patients. Med Sci Monit 2020; 26:e919272. [PMID: 32098942 PMCID: PMC7060510 DOI: 10.12659/msm.919272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Osteosarcoma, the most common solid malignancy, has high incidence and mortality rates. We constructed a miRNA-based signature that can be used to assess the prognosis of osteosarcoma patients. Material/Methods The miRNA profile was derived from the Gene Expression Omnibus (GEO) website, with matched clinical records. The miRNA-based overall survival (OS)-predicting signature was established by LASSO Cox regression analysis. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) analyses were performed to examine the stability and discriminatory ability of the OS-predicting signatures. Pathway enrichment analyses were performed to uncover potential mechanisms. Results Three miRNAs (miR-153, miR-212, and miR-591) independently related to the OS were extracted to build a risk score formula. The ROC curve and K-M analyses revealed good discrimination ability of the OS signature for osteosarcoma patients in both the training cohort (P=0.00015, AUC=0.962) and the validation cohort (P=0.0065, AUC=0.793). As shown in multivariate analysis, the classifier showed favorable predictive accuracy similar to the recurrence status to be an independent risk factor for osteosarcoma. Furthermore, the nomogram showed a synergistic effect by combining the clinicopathological features with our classifier. Also, the enrichment analyses of the target genes may contribute to improved treatment of osteosarcoma. Conclusions The 3-miRNA-based classifier serves as an effective prognosis-predicting signature for osteosarcoma patients.
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Affiliation(s)
- Xinle Luo
- Department of Trauma and Joint Orthopedics, The People's Hospital of Longhua, Shenzhen, Guangdong, China (mainland)
| | - Jiuyang Tang
- Department of Trauma and Joint Orthopedics, The People's Hospital of Longhua, Shenzhen, Guangdong, China (mainland)
| | - Huabing Xuan
- Department of Trauma and Joint Orthopedics, The People's Hospital of Longhua, Shenzhen, Guangdong, China (mainland)
| | - Jianlin Liu
- Department of Trauma and Joint Orthopedics, The People's Hospital of Longhua, Shenzhen, Guangdong, China (mainland)
| | - Xi Li
- Department of Trauma and Joint Orthopedics, The People's Hospital of Longhua, Shenzhen, Guangdong, China (mainland)
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Tavakolian S, Goudarzi H, Torfi F, Faghihloo E. Evaluation of microRNA-9 and -192 expression levels as biomarkers in patients suffering from breast cancer. Biomed Rep 2019; 12:30-34. [PMID: 31839947 DOI: 10.3892/br.2019.1257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Accepted: 10/02/2019] [Indexed: 12/18/2022] Open
Abstract
Given the global outbreak of breast cancer and its debilitating effect on women's health, it is not surprising that tremendous efforts have been made with an aim of shedding more light on the mechanisms involved in the pathogenesis of this type of cancer. Among the long list of risk factors associated with this malignancy, recently, the role of microRNAs (miRNAs or miRs) has turned into a hotspot for breast cancer investigations. miRNAs approximately 20 nucleotides in length and are located in either an exon or an intron, playing a role in the regulation of gene expression. In the present study, we extracted RNA from both the serum and cancerous tissue of breast cancer patients and after synthesizing the cDNA, we performed quantitative PCR to determine the expression levels of miR-9 and miR-192. The resulting data revealed that while the mRNA expression level of miR-9 was significantly decreased in the breast cancer tissues, there was no noticeable change in the expression level of this miRNA in the serum samples. Likewise, we found that the marked downregulation of miR-192 was only restricted to the cancerous tissues, but was not found in the serum of patients. Based on the meaningful downregulation of the expression of miR-9 and miR-192, this study provides a plausible framework for these miRNAs as effective biomarkers for breast cancer patients.
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Affiliation(s)
- Shaian Tavakolian
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Farhad Torfi
- Surgical Ward, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
| | - Ebrahim Faghihloo
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
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