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Ali A, Jamieson NB, Khan IN, Chang D, Giovannetti E, Funel N, Frampton AE, Morton J, Sansom O, Evans TRJ, Duthie F, McKay CJ, Samra J, Gill AJ, Biankin A, Oien KA. Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients. Am J Cancer Res 2022; 12:5668-5683. [PMID: 36628279 PMCID: PMC9827095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/27/2022] [Indexed: 01/12/2023] Open
Abstract
Despite progress in genomic characterization, no single prognostic marker that can be evaluated using an easy-to-perform and relatively inexpensive method is available for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs, which are stable, tumor- and tissue-specific molecules, are potentially ideal biomarkers, and we established an inter-laboratory validated method to investigate miR-21 as a prognostic biomarker in PDAC. The study samples of PDAC patients were recruited from a test cohort of Glasgow (n = 189) and three validation cohorts of Pisa (n = 69), Sydney (n = 249), and International Cancer Genome Consortium (ICGC) (n = 249). Tissue microarrays were used for miR-21 staining by chromogenic in situ hybridization (CISH). The patients were subdivided into no/low and high miR-21 staining groups using a specific histoscore. Furthermore, miR-21 staining was evaluated against clinicopathological variables and follow-up data by Fisher/log-rank test and Cox proportional models. The prognostic variables found to be significant in univariate analysis (P value < 0.10) were included in multivariate analysis in a backward-stepwise fashion. MiR-21 expression was cytoplasmic, with more consistent staining in the malignant ductal epithelium than in the stroma. The expression of miR-21 was significantly associated with tumor size and lymph node metastasis, whereas no association was observed with other clinicopathological variables. High miR-21 staining (histoscore ≥ 45 [median score]) was an independent predictor of survival in the Glasgow test cohort (HR 2.37, 95% CI: 1.42-3.96, P < 0.0001) and three validation cohorts (Pisa, HR 2.03, 95% CI: 1.21-3.39, P = 0.007; Sydney, HR 2.58, 95% CI (1.21-3.39), P < 0.0001; and ICGC, HR 3.34, 95% CI: 2.07-5.84, P = 0.002) when adjusted for clinical variables in a multivariate model. In comparison to the patients with low miR-21, the patients with high miR-21 expression had significant increase in OS as they benefit from gemcitabine-based adjuvant chemotherapy (Glasgow 16.5 months [with chemotherapy] vs 10.5 months [without chemotherapy]); Sydney 25.0 vs 10.6; ICGC 25.2 vs 11.9. These results indicated that miR-21 is a predictor of survival, prompting prospective trials. Evaluation of miR-21 offers new opportunities for the stratification of patients with PDAC and might facilitate the implementation of clinical management and therapeutic interventions for this devastating disease.
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Affiliation(s)
- Asif Ali
- Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowUK
- Institute of Pathology and Diagnostic Medicine, Khyber Medical UniversityPeshawar, Pakistan
- Gulf Medical UniversityAjman, United Arab Emirates
| | - Nigel Balfour Jamieson
- Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowUK
| | - Ishaq N Khan
- Department of Pharmaceutical Sciences, Texas A&M Health Science Center, Joe H. Reynolds Medical Bld, Texas A&M University, College StationUnited States
- Cancer Cell Culture & Precision Oncomedicine Lab, Institute of Basic Medical Sciences, Khyber Medical UniversityPeshawar, Pakistan
| | - David Chang
- Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowUK
| | - Elisa Giovannetti
- Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical CenterAmsterdam, The Netherlands
- Cancer Pharmacology Lab, AIRC Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaPisa, Italy
| | - Nicola Funel
- Cancer Pharmacology Lab, AIRC Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaPisa, Italy
| | - Adam E Frampton
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital CampusDu Cane Road, London, UK
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County HospitalEgerton Road, Guildford, Surrey, GU2 7XX, UK
- Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of SurreyGuildford, Surrey, UK
| | - Jennifer Morton
- Beatson Institute for Cancer Research, University of GlasgowUK
| | - Owen Sansom
- Beatson Institute for Cancer Research, University of GlasgowUK
| | | | - Fraser Duthie
- Department of Pathology, Laboratory Medicine Building, Queen Elizabeth University HospitalGreater Glasgow & Clyde NHS
| | - Colin J McKay
- West of Scotland Pancreatic Unit and Glasgow Royal InfirmaryAlexandra Parade, Glasgow
| | - Jas Samra
- Department of Upper Gastrointestinal Surgery, Royal North Shore HospitalPacific Highway St Leonards, Australia
| | - Anthony J Gill
- Sydney Medical School, University of SydneySydney, Australia
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, and Health Pathology Department of Anatomical Pathology, Royal North Shore HospitalSt Leonards, NSW, Australia
- The Kinghorn Cancer Centre, The Garvan Institute of Medical ResearchDarlinghurst, Sydney, Australia
- The Australian Pancreatic Genome InitiativeDarlinghurst NSW 2010, Australia
| | - Andrew Biankin
- Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowUK
| | - Karin A Oien
- Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of GlasgowUK
- Department of Pathology, Laboratory Medicine Building, Queen Elizabeth University HospitalGreater Glasgow & Clyde NHS
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Davey MG, Feeney G, Annuk H, Paganga M, Holian E, Lowery AJ, Kerin MJ, Miller N. MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer. Cancers (Basel) 2022; 14:cancers14092109. [PMID: 35565239 PMCID: PMC9106021 DOI: 10.3390/cancers14092109] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/13/2022] [Accepted: 04/20/2022] [Indexed: 12/12/2022] Open
Abstract
Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making.
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Affiliation(s)
- Matthew G. Davey
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
- Correspondence:
| | - Gerard Feeney
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
| | - Heidi Annuk
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
| | - Maxwell Paganga
- School of Mathematical and Statistical Sciences, National University of Ireland, H91 H3CY Galway, Ireland; (M.P.); (E.H.)
| | - Emma Holian
- School of Mathematical and Statistical Sciences, National University of Ireland, H91 H3CY Galway, Ireland; (M.P.); (E.H.)
| | - Aoife J. Lowery
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
| | - Michael J. Kerin
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
| | - Nicola Miller
- Department of Surgery, Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (G.F.); (H.A.); (A.J.L.); (M.J.K.); (N.M.)
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Ranjbar R, Ghasemian M, Maniati M, Hossein Khatami S, Jamali N, Taheri-Anganeh M. Gastrointestinal disorder biomarkers. Clin Chim Acta 2022; 530:13-26. [DOI: 10.1016/j.cca.2022.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 01/19/2023]
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Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression. Cancers (Basel) 2022; 14:cancers14020264. [PMID: 35053428 PMCID: PMC8773769 DOI: 10.3390/cancers14020264] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/24/2021] [Accepted: 12/29/2021] [Indexed: 12/22/2022] Open
Abstract
MicroRNA-21 (miR-21) is a small, non-coding RNA overexpressed in gastric cancer and many other solid malignancies, where it exhibits both pro-and anti-tumourigenic properties. However, the pathways regulating miR-21 and the consequences of its inhibition in gastric cancer remain incompletely understood. By exploiting the spontaneous Stat3-dependent formation of inflammation-associated gastric tumors in Gp130F/F mice, we functionally established miR-21 as a Stat3-controlled driver of tumor growth and progression. We reconciled our discoveries by identifying several conserved Stat3 binding motifs upstream of the miR-21 gene promoter, and showed that the systemic administration of a miR-21-specific antisense oligonucleotide antagomir reduced the established gastric tumor burden in Gp130F/F mice. We molecularly delineated the therapeutic benefits of miR-21 inhibition with the functional restoration of PTEN in vitro and in vivo, alongside an attenuated epithelial-to-mesenchymal transition and the extracellular matrix remodeling phenotype of tumors. We corroborated our preclinical findings by correlating high STAT3 and miR-21 expression with the reduced survival probability of gastric cancer patients. Collectively, our results provide a molecular framework by which miR-21 mediates inflammation-associated gastric cancer progression, and establish miR-21 as a robust therapeutic target for solid malignancies characterized by excessive Stat3 activity.
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Nguyen HT, Kacimi SEO, Nguyen TL, Suman KH, Lemus-Martin R, Saleem H, Do DN. MiR-21 in the Cancers of the Digestive System and Its Potential Role as a Diagnostic, Predictive, and Therapeutic Biomarker. BIOLOGY 2021; 10:biology10050417. [PMID: 34066762 PMCID: PMC8151274 DOI: 10.3390/biology10050417] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/27/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.
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Affiliation(s)
- Ha Thi Nguyen
- Institute of Research and Development, Duy Tan University, Danang 550000, Vietnam;
- Faculty of Medicine, Duy Tan University, Danang 550000, Vietnam
| | | | - Truc Ly Nguyen
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;
| | - Kamrul Hassan Suman
- Department of Fisheries Biology & Aquatic Environment, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh;
| | | | - Humaira Saleem
- Jamil–ur–Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;
| | - Duy Ngoc Do
- Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS B2N5E3, Canada
- Correspondence: ; Tel.: +1-819-571-5310
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Feng Y, Shu J, Yao L, Lan Y, Ye L, Mei W, Ding Y. Recognizing and stabilizing miR-21 by chiral ruthenium(II) complexes. BMC Chem 2020; 14:26. [PMID: 32266333 PMCID: PMC7119291 DOI: 10.1186/s13065-020-00672-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 03/09/2020] [Indexed: 12/19/2022] Open
Abstract
MiR-21, a non-coding miRNA with 22 nucleotides, plays an important part in the proliferation, invasion, and metastasis of tumor cells. The present study demonstrates that isomers of chiral ruthenium(II) complexes with alkynes (Λ-1 and Δ-1) were synthesized by Songogashira coupling reaction by using microwave-assisted synthetic technology. The isomers can recognize and stabilize miR-21, with the Λ-isomer showing a stronger binding capacity than the Δ-isomer. Further studies showed that both isomers can be uptaken by MDA-MB-231 cells and enriched in the nucleus. Treatment with the Λ-/Δ-isomer downregulated the expression of miR-21. In a word, the development of chiral ruthenium(II) complexes act as potential inhibitors against tumor cells by recognizing, stabilizing, and regulating the expression of miR-21.
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Affiliation(s)
- Yin Feng
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510062 China
| | - Jing Shu
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006 China
- Guangdong Province Engineering Center for Molecular Probe & Biomedical Imaging, Guangzhou, 510006 China
| | - Liangzhong Yao
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510062 China
| | - Yutao Lan
- Guangdong Province Engineering Center for Molecular Probe & Biomedical Imaging, Guangzhou, 510006 China
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006 China
| | - Lianbao Ye
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006 China
- Guangdong Province Engineering Center for Molecular Probe & Biomedical Imaging, Guangzhou, 510006 China
- Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model System, Guangdong Pharmaceutical University, Guangzhou, 510006 China
| | - Wenjie Mei
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006 China
- Guangdong Province Engineering Center for Molecular Probe & Biomedical Imaging, Guangzhou, 510006 China
- Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model System, Guangdong Pharmaceutical University, Guangzhou, 510006 China
| | - Ying Ding
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510062 China
- Guangdong Province Engineering Center for Molecular Probe & Biomedical Imaging, Guangzhou, 510006 China
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Xu M, Fu P, Xing S, Zhao Y, Zhao C. A PNA-DNA 2 Triple-Helix Molecular Switch-Based Colorimetric Sensor for Sensitive and Specific Detection of microRNAs from Cancer Cells. Chembiochem 2020; 21:2667-2675. [PMID: 32304168 DOI: 10.1002/cbic.202000155] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/16/2020] [Indexed: 01/07/2023]
Abstract
Peptide nucleic acids (PNAs), the synthetic DNA mimics that can bind to oligonucleotides to form duplexes, triplexes, and quadruplexes, could be advantageous as probes for nucleic acid sequences owing to their unique physicochemical and biochemical properties. We have found that a homopurine PNA strand could bind to two homopyrimidine DNA strands to form a PNA-DNA2 triplex. Moreover, the cyanine dye DiSC2 (5) could bind with high affinity to this triplex and cause a noticeable color change. On the basis of this phenomenon, we have designed a label-free colorimetric sensing platform for miRNAs from cancer cells by using a PNA-DNA2 triple-helix molecular switch (THMS) and DiSC2 (5). This sensing platform can detect miRNA-21 specifically with a detection limit of 0.18 nM, which is comparable to that of the THMS-mediated fluorescence sensing platform. Moreover, this colorimetric platform does not involve any chemical modification or enzymatic signal amplification, which boosts its applicability and availability at the point of care in resource-limited settings. The universality of this approach can be simply achieved by altering the sequences of the probe DNA for specific targets.
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Affiliation(s)
- Mengjia Xu
- Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.,University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Pan Fu
- Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.,University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Shu Xing
- Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China
| | - Yang Zhao
- College of Science and Technology, Ningbo University, Ningbo, 315212, P. R. China
| | - Chao Zhao
- Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China
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Ahadi A. Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression. IUBMB Life 2020; 72:884-898. [DOI: 10.1002/iub.2259] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 02/08/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Alireza Ahadi
- Department of Medical Genetics, School of MedicineShahid Beheshti University of Medical Sciences Tehran Iran
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Ding L, Lu S, Li Y. Regulation of PD-1/PD-L1 Pathway in Cancer by Noncoding RNAs. Pathol Oncol Res 2020; 26:651-663. [PMID: 31748880 DOI: 10.1007/s12253-019-00735-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 08/27/2019] [Indexed: 12/24/2022]
Abstract
Immune checkpoint blockade has demonstrated significant anti-tumor immunity in an array of cancer types, yet the underlying regulatory mechanism of it is still obscure, and many problems remain to be solved. As an inhibitory costimulatory signal of T-cells, the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway can paralyze T-cells at the tumor site, enabling the immune escape of tumor cells. Although many antibodies targeting PD-1/PD-L1 have been developed to block their interaction for the treatment of cancer, the reduced response rate and resistance to the therapies call for further comprehension of this pathway in the tumor microenvironment. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main types of noncoding RNAs that play critical parts in the regulation of immune response in tumorigenesis, including the PD-1/PD-L1 pathway. Here we summarize the most recent studies on the control of this pathway by noncoding RNAs in cancer and hopefully will offer new insights into immune checkpoint blockade therapies.
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Affiliation(s)
- Lei Ding
- Lab for Noncoding RNA & Cancer, School of Life Science, Shanghai University, Shanghai, 200444, China
| | - Shengdi Lu
- Shanghai Sixth People's Hospital, affiliated to Shanghai Jiao Tong University, Shanghai, 200233, China.
| | - Yanli Li
- Lab for Noncoding RNA & Cancer, School of Life Science, Shanghai University, Shanghai, 200444, China.
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Yao L, Shi W, Gu J. Micro-RNA 205-5p is Involved in the Progression of Gastric Cancer and Targets Phosphatase and Tensin Homolog (PTEN) in SGC-7901 Human Gastric Cancer Cells. Med Sci Monit 2019; 25:6367-6377. [PMID: 31444971 PMCID: PMC6724565 DOI: 10.12659/msm.915970] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background This study aimed to investigate the role of micro-RNA 205-5p (miR-205-5p) in the progression of gastric cancer, and the target of miR-205-5p in human gastric cancer cells in vitro. Material/Methods Expression of miR-205-5p and PTEN in gastric cancer tissue samples and adjacent normal gastric tissue from 35 patients was studied using immunohistochemistry and in situ hybridization. SGC-7901 human gastric cancer cells included a normal control (NC) group, a group transfected with empty vector (Vector), a group treated with miR-205-5p inhibitor (miR-inhibitor), and a group treated with miR-205-5p inhibitor and small interfering PTEN mRNA (miR-inhibitor+si-PTEN). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measured miR-205-5p expression, cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry, transwell and wound healing assays measured cell migration, and transmission electron microscopy (TEM) showed ultrastructural changes in SGC-7901 cells. PTEN, AKT and p-AKT protein expression were measured using Western blot. The correlation between miR-205-5p and PTEN was analyzed using a dual-luciferase reporter assay. Results Increased expression of miR-205-5p and PTEN in gastric cancer tissues were correlated with tumor stage. In SGC-7901 cells, miR-205-5p mRNA expression in the miR-inhibitor and miR-inhibitor+si-PTEN groups was significantly lower than that in the NC group (P<0.001). In the miR-inhibitor group, cell proliferation was significantly decreased, and apoptosis was significantly increased (P<0.001). Conclusions In gastric cancer, increased expression of miR-205-5p was associated with tumor stage, and in SGC-7901 cells PTEN was a target gene for miR-205-5p.
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Affiliation(s)
- Lina Yao
- Department of Clinical Laboratory, The First People's Hospital of Changzhou, Changzhou, Jiangsu, Chile
| | - Weifeng Shi
- Department of Clinical Laboratory, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China (mainland)
| | - Jianwen Gu
- Department of Clinical Laboratory, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China (mainland)
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Zhang Y, Guan DH, Bi RX, Xie J, Yang CH, Jiang YH. Prognostic value of microRNAs in gastric cancer: a meta-analysis. Oncotarget 2017; 8:55489-55510. [PMID: 28903436 PMCID: PMC5589675 DOI: 10.18632/oncotarget.18590] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous articles have reported that expression levels of microRNAs (miRNAs) are associated with survival time of patients with gastric cancer (GC). A systematic review and meta-analysis was performed to study the outcome of it. DESIGN Meta-analysis. METHODS English studies estimating expression levels of miRNAs with any of survival curves in GC were identified up till March 19, 2017 through performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two authors independently. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS). RESULTS Sixty-nine relevant articles about 26 miRNAs with 6148 patients were ultimately included. GC patients with high expression of miR-20b (HR=2.38, 95%CI=1.16-4.87), 21 (HR=1.77, 95%CI=1.01-3.08), 106b (HR=1.84, 95%CI=1.15-2.94), 196a (HR=2.66, 95%CI=1.94-3.63), 196b (HR=1.67, 95%CI=1.38-2.02), 214 (HR=1.84, 95%CI=1.27-2.67) or low expression of miR-125a (HR=2.06, 95%CI=1.26-3.37), 137 (HR=3.21, 95%CI=1.68-6.13), 141 (HR=2.47, 95%CI=1.34-4.56), 145 (HR=1.62, 95%CI=1.07-2.46), 146a (HR=2.60, 95%CI=1.63-4.13), 206 (HR=2.85, 95%CI=1.73-4.70), 218 (HR=2.61, 95%CI=1.74-3.92), 451 (HR=1.73, 95%CI=1.19-2.52), 486-5p (HR=2.45, 95%CI=1.65-3.65), 506 (HR=2.07, 95%CI=1.33-3.23) have significantly poor OS (P<0.05). CONCLUSIONS In summary, miR-20b, 21, 106b, 125a, 137, 141, 145, 146a, 196a, 196b, 206, 214, 218, 451, 486-5p and 506 demonstrate significantly prognostic value. Among them, miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p and 506 are strong biomarkers of prognosis in GC.
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Affiliation(s)
- Yue Zhang
- 1 First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, People's Republic of China
| | - Dong-Hui Guan
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Rong-Xiu Bi
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Jin Xie
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Chuan-Hua Yang
- 3 Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Yue-Hua Jiang
- 4 Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
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Zheng Q, Chen C, Guan H, Kang W, Yu C. Prognostic role of microRNAs in human gastrointestinal cancer: A systematic review and meta-analysis. Oncotarget 2017; 8:46611-46623. [PMID: 28402940 PMCID: PMC5542297 DOI: 10.18632/oncotarget.16679] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 03/09/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Gastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high mortality worldwide. We performed this systematic review and meta-analysis to elucidate relationship between multiple microRNAs (miRs) expression and survival of GIC patients. METHODS We searched a wide range of database. Fixed-effects and random-effects models were used to calculate the pooled hazard ratio values of overall survival and disease free survival. In addition, funnel plots were used to qualitatively analyze the publication bias and verified by Begg's test while it seems asymmetry. RESULTS 60 studies involving a total of 6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517 with colorectal cancer) were included in our meta-analysis. The pooled hazard ratio values of overall survival related to different miRs expression in esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78-2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor prognosis in GIC patients. Moreover, 35 of them revealed mechanisms. CONCLUSION Overall, specific miRs are significantly associated with the prognosis of GIC patients and potentially eligible for the prediction of patients survival. It also provides a potential value for clinical decision-making development and may serve as a promising miR-based target therapy waiting for further elucidation.
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Affiliation(s)
- Qiang Zheng
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Changyu Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Traditional Medical University, Hefei, China
| | - Haiyang Guan
- Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China
| | - Weibiao Kang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Changjun Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
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13
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Sekar D, Krishnan R, Thirugnanasambantham K, Rajasekaran B, Islam VIH, Sekar P. Significance of microRNA 21 in gastric cancer. Clin Res Hepatol Gastroenterol 2016; 40:538-545. [PMID: 27179559 DOI: 10.1016/j.clinre.2016.02.010] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 02/01/2016] [Accepted: 02/17/2016] [Indexed: 02/04/2023]
Abstract
Despite promising developments of treatment, the mortality due to gastric cancer remains high and the mechanisms of gastric cancer initiation and the development also remains elusive. It has been reported that patients with positive serologic tests for H. pylori have a higher risk of the development of gastric cancer. microRNAs (miRNAs) are short non-coding RNA molecules consisting of 21-25 nucleotides (nt) in length. The miRNAs silence their cognate target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3'-untranslated (UTR) regions and plays a very important role in cancer biology. Recent evidences indicate that miR-21 is overexpressed in tumour tissue, including gastric cancer and plays a vital role in tumour cell proliferation, apoptosis, invasion and angiogenesis. Elevated levels of miR-21 is associated with downregulation of tumour suppressor genes, such as programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3, phosphatase and tensin homolog (PTEN), tropomyosin 1, ras homolog gene family member B, and maspin. Silencing of miR-21 through the use of a miR-21 inhibitor affected cancer cell viability, induced cell cycle arrest and increased chemosensitivity to anticancer agents indicating that miR-21 functions as an oncogene. Although an increased expression level of miR-21 has been observed in gastric cancer, studies related to the role of miR-21 in gastric cancer progression is very limited. The main thrust of this mini review is to explain the potency of miR-21 as a prognostic and/or diagnostic biomarker and as a new target for clinical therapeutic for interventions of gastric cancer progression.
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Affiliation(s)
- Durairaj Sekar
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India; Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India.
| | - Ramalingam Krishnan
- Narayana Medical College and Hospital, Chintha Reddy Palem, Nellore 524002, India
| | | | - Baskaran Rajasekaran
- Biochemistry and Molecular Biology, Pondicherry University, RV Nagar, Pondicherry 6-5014, India
| | | | - Punitha Sekar
- Stem Cell Division, Cryovault Biotech India Pvt. Ltd, Bangalore 560016, India
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14
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Mao XH, Chen M, Wang Y, Cui PG, Liu SB, Xu ZY. MicroRNA-21 regulates the ERK/NF-κB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN. Mol Carcinog 2016; 56:886-894. [PMID: 27533779 DOI: 10.1002/mc.22542] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 08/02/2016] [Accepted: 08/15/2016] [Indexed: 12/19/2022]
Abstract
This study aims to explore the effects of microRNA-21 (miR-21) and ERK/NF-κB signaling pathway on human melanoma A375 cells. The melanoma tissues and adjacent normal tissues were obtained from 45 melanoma patients. qRT-PCR was conducted to quantify the expression of miR-21 and the gene mRNA expressions. Human melanoma A375 cells were divided into the Mock, negative control (NC), miR-21 inhibitors, miR-21 inhibitors + siRNA-SPRY1, miR-21 inhibitors + siRNA-PDCD4, and miR-21 inhibitors + siRNA-PTEN groups. Western blotting was used to determine protein expressions. CCK8 assay and Transwell assay were performed to evaluate the proliferation, migration, and invasion of A375 cells. Annexin V/propidium iodide double staining was adopted to detect cell apoptosis. MiR-21 expression was higher in melanoma tissues than in adjacent tissues, while the mRNA and protein expressions of SPRY1, PDCD4, and PTEN were lower in melanoma tissues than in adjacent tissues. Compared with the Mock and NC groups, the miR-21 inhibitors group exhibited increased expressions of SPRY1, PDCD4, and PTEN and decreased expressions of ERK, p-ERK, NF-κB p65, and p-NF-κB p65. After transfection of miR-21 inhibitors, the proliferation, migration, and invasion of A375 cells were inhibited, while the apoptosis of A375 cells was promoted. However, the effects of miR-21 inhibitors on the growth, migration, invasion, and apoptosis of A375 cells were reversed after transfection of siRNA-SPRY1, siRNA-PDCD4, or siRNA-PTEN. MiR-21 can promote the proliferation, migration, and inhibit the apoptosis of human melanoma A375 cells by inhibiting SPRY1, PDCD4, and PTEN via ERK/NF-κB signaling pathway. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Xu-Hua Mao
- Department of Clinical Laboratory, Yixing People's Hospital, Wuxi, P.R. China
| | - Min Chen
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, P.R. China
| | - Yan Wang
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, P.R. China
| | - Pan-Gen Cui
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, P.R. China
| | - Si-Bian Liu
- Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin Province, P.R. China
| | - Zei-Yong Xu
- Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin Province, P.R. China
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15
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da Silva Oliveira KC, Thomaz Araújo TM, Albuquerque CI, Barata GA, Gigek CO, Leal MF, Wisnieski F, Rodrigues Mello Junior FA, Khayat AS, de Assumpção PP, Rodriguez Burbano RM, Smith MC, Calcagno DQ. Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol 2016; 22:7951-7962. [PMID: 27672290 PMCID: PMC5028809 DOI: 10.3748/wjg.v22.i35.7951] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Revised: 06/14/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity.
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16
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Tsai MM, Wang CS, Tsai CY, Huang HW, Chi HC, Lin YH, Lu PH, Lin KH. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer. Int J Mol Sci 2016; 17:945. [PMID: 27322246 PMCID: PMC4926478 DOI: 10.3390/ijms17060945] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/01/2016] [Accepted: 06/07/2016] [Indexed: 12/11/2022] Open
Abstract
Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients' survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.
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Affiliation(s)
- Ming-Ming Tsai
- Department of Nursing, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan.
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
| | - Chia-Siu Wang
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
| | - Chung-Ying Tsai
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Hsiang-Wei Huang
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Hsiang-Cheng Chi
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Yang-Hsiang Lin
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
| | - Pei-Hsuan Lu
- Department of Dermatology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
| | - Kwang-Huei Lin
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
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17
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Treece AL, Duncan DL, Tang W, Elmore S, Morgan DR, Dominguez RL, Speck O, Meyers MO, Gulley ML. Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns. J Transl Med 2016; 96:661-71. [PMID: 26950485 PMCID: PMC5767475 DOI: 10.1038/labinvest.2016.33] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 12/09/2015] [Accepted: 01/12/2016] [Indexed: 12/27/2022] Open
Abstract
MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics.
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MESH Headings
- Adenocarcinoma/genetics
- Adenocarcinoma/metabolism
- Adenocarcinoma/virology
- Aged
- Aged, 80 and over
- Case-Control Studies
- Epstein-Barr Virus Infections/genetics
- Epstein-Barr Virus Infections/metabolism
- Epstein-Barr Virus Infections/virology
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Herpesvirus 4, Human/genetics
- Herpesvirus 4, Human/isolation & purification
- Humans
- Male
- MicroRNAs/blood
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Middle Aged
- Pilot Projects
- RNA, Neoplasm/blood
- RNA, Neoplasm/genetics
- RNA, Neoplasm/metabolism
- RNA, Viral/blood
- RNA, Viral/genetics
- RNA, Viral/metabolism
- Stomach Neoplasms/genetics
- Stomach Neoplasms/metabolism
- Stomach Neoplasms/virology
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Affiliation(s)
- Amanda L Treece
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Daniel L Duncan
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Weihua Tang
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Sandra Elmore
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Douglas R Morgan
- Division of Gastroenterology, Hepatology, and Nutrition; Department of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Ricardo L Dominguez
- Department of Gastroenterology, Western Regional Hospital, Santa Rosa de Copan, Honduras
| | - Olga Speck
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Michael O Meyers
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Margaret L Gulley
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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18
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Li Z, Yu X, Wang Y, Shen J, Wu WKK, Liang J, Feng F. By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget 2016; 6:17559-69. [PMID: 25654811 PMCID: PMC4627328 DOI: 10.18632/oncotarget.2755] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Accepted: 11/16/2014] [Indexed: 01/07/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Emerging evidence has shown that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. MiR-329 was previously reported to act as a tumor suppressor or oncogene in some types of cancer. However, its function in gastric cancer (GC) is unclear. Here, we found that miR-329 was down-regulated in GC compared with adjacent controls. Enforced expression of miR-329 inhibited proliferation, migration and invasion of gastric cancer cells in vitro. We identified T lymphoma invasion and metastasis 1 (TIAM1) gene as potential target of miR-329. MiR-329 levels inversely correlated with TIAM1 expression in GC. Importantly, TIAM1 rescued the miR-329-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-329 significantly inhibited tumor formation of GC in the xenograft mice. Our findings suggest that miR-329 is a tumor suppressor and potential therapeutic target of GC
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Affiliation(s)
- Zheng Li
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Yu
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Wang
- Department of Abdominal Surgery, Cancer Institute and Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jianxiong Shen
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - William Ka Kei Wu
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China
| | - Jinqian Liang
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Feng
- Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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19
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Hu GY, Tao F, Wang W, Ji KW. Prognostic value of microRNA-21 in pancreatic ductal adenocarcinoma: a meta-analysis. World J Surg Oncol 2016; 14:82. [PMID: 26969625 PMCID: PMC4786997 DOI: 10.1186/s12957-016-0842-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 03/08/2016] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Recently, microRNA-21 (miR-21) has been reported to be associated with prognosis of pancreatic ductal adenocarcinoma (PDAC). The present studies aimed to evaluate the prognostic value of miR-21 for PDAC with meta-analysis. METHODS A systematic search in the PubMed and other databases was conducted to identify eligible studies. The pooled hazard ratios (HRs) with 95% confidence interval (CI) were calculated. The meta-analysis was conducted using the STATA 12.0 software. RESULTS A total of 12 articles (13 studies) which included 963 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 2.05, 95% CI 1.71-2.46, P < 0.001). In the subgroup analyses, similar results were observed in Asian (HR = 2.09, 95% CI 1.62-2.71, P < 0.001) and Caucasian (HR = 2.36, 95% CI 1.53-3.65, P < 0.001); in tissue sample (HR = 2.14, 95% CI 1.73-2.65, P < 0.001) and serum sample (HR = 1.84, 95% CI 1.30-2.60, P = 0.001); with quantitative real-time polymerase chain reaction assay method (HR = 2.31, 95% CI 1.86-2.86, P < 0.001); and in patients receiving adjuvant chemotherapy (HR = 2.37, 95% CI 1.88-3.00, P < 0.001). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 1.45, 95% CI 1.02-2.06, P = 0.038). However, no significant relationship between miR-21 expression level and sex or vascular invasion or neural infiltration was observed (P > 0.05). CONCLUSIONS Our meta-analysis indicated that elevated miR-21 expression level can predict poor prognosis in patients with PDAC.
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Affiliation(s)
- Geng-yuan Hu
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Road, Shaoxing, 312000, China
| | - Feng Tao
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Road, Shaoxing, 312000, China
| | - Wei Wang
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Road, Shaoxing, 312000, China.
| | - Ke-wei Ji
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Road, Shaoxing, 312000, China
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20
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Yan W, Qian L, Chen J, Chen W, Shen B. Comparison of Prognostic MicroRNA Biomarkers in Blood and Tissues for Gastric Cancer. J Cancer 2016; 7:95-106. [PMID: 26722365 PMCID: PMC4679386 DOI: 10.7150/jca.13340] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Accepted: 10/18/2015] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) still keeps up high mortality worldwide with poor prognosis. Efficient and non-invasive prognostic biomarkers are urgently needed. MicroRNAs are non-coding RNAs playing roles in post-transcriptional gene regulation, which contribute to various biological processes such as development, differentiation and carcinogenesis. MicroRNA expression profiles have been associated with the prognosis and outcome in GC. MicroRNA prognostic biomarkers have been identified from blood or tissues samples, but with different prognostic features. Understanding the various roles of microRNAs in different sample sources of GC will provide deep insights into GC progression. In this review, we highlight the distinct prognostic roles of microRNAs biomarkers in blood and tissue according to their relationships with prognostic parameters, survival rates and target pathways. This will be useful for non-invasive biomarker development and selection in prognosis of GC.
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Affiliation(s)
- Wenying Yan
- 1. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; ; 2. Taicang Center for Translational Bioinformatics, Taicang 215400, China; ; 3. Center for Systems Biology, Soochow University, Suzhou 215006, China
| | - Laijun Qian
- 4. Daibu Center Hospital, Liyang, 213330, China
| | - Jiajia Chen
- 5. School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215011, China
| | - Weichang Chen
- 1. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Bairong Shen
- 3. Center for Systems Biology, Soochow University, Suzhou 215006, China
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21
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Liu L, Ye JX, Qin YZ, Chen QH, Ge LY. Evaluation of miR-29c, miR-124, miR-135a and miR-148a in predicting lymph node metastasis and tumor stage of gastric cancer. Int J Clin Exp Med 2015; 8:22227-22236. [PMID: 26885198 PMCID: PMC4729984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 12/12/2015] [Indexed: 06/05/2023]
Abstract
MicroRNAs (miRNAs) are small noncoding RNA that have diverse functions in different biological process. The aim of this study was to evaluate the predictive ability of miR-29c, miR-124, miR-135a and miR-148a for lymph node metastasis (LNM) and tumor stage in gastric cancer. The expression of these miRNAs was detected and quantitated in gastric cancer tissues and in adjacent normal tissues from 60 patients by quantitative real-time reverse transcription-polymerase chain reaction. CT imaging and clinicopathologic characteristics of these patients were performed. The result of this study was that these miRNAs were down-regulated in gastric cancer tissues; The low expression of miR-124 and miR-135a in LNM group and tumor III-IV stages (P < 0.01) presented the potential correlation with LNM and tumor stage; The two miRNAs were highly correlated with r = 0.730. Receiver operating characteristic curve analysis showed that miR-124 had better predictive ability to identify LNM and tumor stage. It could discriminate non-LNM from LNM with 80.0% sensitivity and 80.0% specificity and discriminate tumor Ι-II stages from tumor III-IV stages with 71.9% sensitivity and 75.0% specificity at the best cut-off value of 0.0125. Compared with CT imaging, miR-124 had similar specificity (0.800 versus 0.900, P = 0.508) but higher sensitivity (0.800 versus 0.500, P = 0.022) for lymph node assessment; Combined of miR-124 and CT imaging, The sensitivity and specificity of assessing LNM were raised to 83.3% and 90.0% respectively. Taken together, miR-124 may be a predictor for LNM and tumor stage in gastric cancer.
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Affiliation(s)
- Li Liu
- Department of Medical Oncology, The Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Jia-Xiang Ye
- Department of Medical Oncology, The Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Yu-Zhou Qin
- Department of Gastrointestinal Surgery, The Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Qi-Huang Chen
- Department of Medical Oncology, The Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Lian-Ying Ge
- Department of Medical Oncology, The Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
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22
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Li J, Jin Y, Pan S, Chen Y, Wang K, Lin C, Jin S, Wu J. TCEA3 Attenuates Gastric Cancer Growth by Apoptosis Induction. Med Sci Monit 2015; 21:3241-6. [PMID: 26498664 PMCID: PMC4627366 DOI: 10.12659/msm.895860] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Background The aim of this study was to investigate and interpret the expression level and potential function of TCEA3 in gastric cancer. Material/Methods qRT-PCR was used to determine the expression level of TCEA3 in gastric cancer tissues. Pearson χ2 test was performed to clarify the correlation between TCEA3 expression and patients’ clinicopathologic characteristics. Biological function of TCEA3 was tested by proliferation assay and colony formation assay. Flow cytometry was used to study the potential function of TCEA3 in apoptosis induction. Results TCEA3 expression was significantly downregulated in gastric cancer tissues compared with paired normal tissues. Poor prognoses were observed in the low TCEA3 expression group of patients in contrast to the high TCEA3 expression group. Functionally, upregulation of TCEA3 inhibited gastric cancer cell proliferation and colony formation. We also found that TCEA3 may attenuate cell growth through apoptosis induction. Conclusions Our findings suggest that TCEA3 attenuates the proliferation and induces apoptosis of gastric cancer cells.
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Affiliation(s)
- Jia Li
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Yin Jin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Shuang Pan
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Yina Chen
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Kaijing Wang
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Chunjing Lin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Shuqing Jin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Jiansheng Wu
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
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Yang Q, Zhang RW, Sui PC, He HT, Ding L. Dysregulation of non-coding RNAs in gastric cancer. World J Gastroenterol 2015; 21:10956-10981. [PMID: 26494954 PMCID: PMC4607897 DOI: 10.3748/wjg.v21.i39.10956] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/28/2015] [Accepted: 09/15/2015] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC.
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Wu X, Tan X, Fu SW. May Circulating microRNAs be Gastric Cancer Diagnostic Biomarkers? J Cancer 2015; 6:1206-13. [PMID: 26535061 PMCID: PMC4622850 DOI: 10.7150/jca.12535] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 08/25/2015] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related deaths. More than 80% of the diagnosis was made at the advanced stages of the disease, highlighting the urgent demand for novel biomarkers that can be used for early detection. Recently, a number of studies suggest that circulating microRNAs (miRNAs) could be potential biomarkers for GC diagnosis. Cancer-related circulating miRNAs, as well as tissue miRNAs, provide a hopeful prospect of detecting GC at early stages, and the prospective participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic tests for GC. As miRNAs in blood are stable, their potential value as diagnostic biomarkers in GC has been explored over the past few years. However, due to the inconsistent or sometimes conflicting reports, large-scale prospective studies are needed to validate their potential applicability in GC diagnosis. This review summarizes the current development about potential miRNA biomarkers for GC diagnosis and the obstacles hindering their clinical usage.
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Affiliation(s)
- Xiaoling Wu
- 1. Department of Gastroenterology, Chengdu Military General Hospital, Chengdu, China
- 2. Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC
| | - Xiaohui Tan
- 2. Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC
| | - Sidney W. Fu
- 2. Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC
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25
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Effatpanah H, Yadegarazari R, Karami M, Majlesi A, Shabab N, Saidijam M. Expression Analysis of mir-21 and mir-221 in Cancerous Tissues from Iranian Patients with Gastric Cancer. IRANIAN BIOMEDICAL JOURNAL 2015; 19:188-193. [PMID: 26209976 PMCID: PMC4649853 DOI: 10.7508/ibj.2015.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Revised: 10/20/2014] [Accepted: 11/04/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND Early detection is a key to survival for gastric cancer. Molecular markers such as miRNA (microRNA) can have great importance in the early diagnosis of gastric cancer. Expression of miR-21 and miR-221 are deregulated in many types of human cancers. This study aimed to investigate the differences in miRNA expression patterns within the Iranian population. METHODS Total RNA was extracted from gastric cancer tissues and adjacent non-cancerous tissues from 32 patients. Expression levels of miR-21 and miR-221 were detected by Real time RT-PCR using a specific primer, with 5s rRNA as the internal reference gene. RESULTS Our data showed that the expression levels of miR-21 and miR-221 in gastric cancer samples were significantly higher than in paired non-cancerous samples (P value less than 0.05). The receiver operating characteristic (ROC) analyses yielded the area under the curve (AUC) values of 80.30 for miR-21 and 93.30 for miR-221, and combined ROC analysis revealed the highest AUC value of 96.90 in discriminating GC patients from healthy controls. CONCLUSION It seems that miR-21 and miR-221 expression pattern in Iranian patients with gastric cancer are similar to any other population. Considering the increased expression level of two miRNAs in cancerous tissue compared to normal tissue as well as the area under ROC curve, miR-21 and miR-221 can be used for early detection of gastric cancer.
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Affiliation(s)
- Hosein Effatpanah
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
- Dept. of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
| | - Reza Yadegarazari
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
- Dept. of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
| | - Manoochehr Karami
- Social Determinant of Health Research Center and Dept. of Biostatistics and Epidemiology, Hamadan University of Medical Sciences, Hamadan, Iran;
| | - Amir Majlesi
- Dept. of Gastrointestinal Disease, Beheshti Hospital of Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nooshin Shabab
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
- Dept. of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
- Dept. of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;
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Darnet S, Moreira FC, Hamoy IG, Burbano R, Khayat A, Cruz A, Magalhães L, Silva A, Santos S, Demachki S, Assumpção M, Assumpção P, Ribeiro-Dos-Santos Â. High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers. Bioinform Biol Insights 2015; 9:1-8. [PMID: 26157332 PMCID: PMC4485834 DOI: 10.4137/bbi.s23773] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 03/29/2015] [Accepted: 04/01/2015] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer has a high incidence and mortality rate worldwide; however, the use of biomarkers for its clinical diagnosis remains limited. The microRNAs (miRNAs) are biomarkers with the potential to identify the risk and prognosis as well as therapeutic targets. We performed the ultradeep miRnomes sequencing of gastric adenocarcinoma and gastric antrum without tumor samples. We observed that a small set of those samples were responsible for approximately 80% of the total miRNAs expression, which might represent a miRNA tissue signature. Additionally, we identified seven miRNAs exhibiting significant differences, and, of these, hsa-miR-135b and hsa-miR-29c were able to discriminate antrum without tumor from gastric cancer regardless of the histological type. These findings were validated by quantitative real-time polymerase chain reaction. The results revealed that hsa-miR-135b and hsa-miR-29c are potential gastric adenocarcinoma occurrence biomarkers with the ability to identify individuals at a higher risk of developing this cancer, and could even be used as therapeutic targets to allow individualized clinical management.
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Affiliation(s)
- Sylvain Darnet
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Fabiano C Moreira
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Área de Ciências Exatas e Tecnológicas, Centro Universitário do Pará, Belém, PA, Brazil
| | - Igor G Hamoy
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Universidade Federal Rural da Amazônia, Campus de Capanema, PA, Brazil
| | - Rommel Burbano
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - André Khayat
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - Aline Cruz
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Leandro Magalhães
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Artur Silva
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
| | - Sidney Santos
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
| | - Samia Demachki
- Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil. ; Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, PA, Brazil
| | - Monica Assumpção
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
| | - Paulo Assumpção
- Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil. ; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
| | - Ândrea Ribeiro-Dos-Santos
- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil
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Jiang C, Chen X, Alattar M, Wei J, Liu H. MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer. Cancer Gene Ther 2015; 22:291-301. [DOI: 10.1038/cgt.2015.19] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 03/15/2015] [Accepted: 03/16/2015] [Indexed: 02/07/2023]
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Omrane I, Benammar-Elgaaied A. The immune microenvironment of the colorectal tumor: Involvement of immunity genes and microRNAs belonging to the TH17 pathway. Biochim Biophys Acta Rev Cancer 2015; 1856:28-38. [PMID: 25911397 DOI: 10.1016/j.bbcan.2015.04.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 03/16/2015] [Accepted: 04/14/2015] [Indexed: 12/17/2022]
Abstract
Colorectal cancer is a complex and multifactorial disease. Various factors such as genetic, immunological, epigenetic and environmental constitute minor risk factors with their additive effects contributing to the advent of colorectal cancer. In order to evaluate the role of innate and adaptive immunity in the susceptibility, the presentation and the development of colorectal cancer, we considered an immunogenetic approach on polymorphisms in the TLR4 gene and NOD2/CARD15 gene (receptors of innate immunity) as well as in cytokine genes of the TH17 pathway IL17A, IL17F and cytokine receptor IL23R. Then, we evaluated the expression of microRNAs regulated by TLR4 and NOD2/CARD15 or targeting TLR4, IL17 and proinflammatory cytokines (IL-6, TNF) induced by IL17. Through a case-control study, we showed that the polymorphism of IL17A is associated with its susceptibility to colorectal cancer. Considering the tumor location, we found that the mutated alleles of IL17A, IL17F and IL23R are rather associated with colon cancer and not with rectum cancer. This result confirms that the colon and rectum are two different physiological entities. This study shows that TLR4, IL17A/F and IL23R polymorphisms are involved in the presentation of the disease with regard to tumor architecture, histology, and differentiation, advanced stage of the disease and lymph node and metastasis. Overall, these polymorphisms are associated with a poor prognosis of the disease. Furthermore, in order to evaluate the involvement of epigenetic mechanisms in the occurrence of colorectal cancer, we aimed at analyzing the tumor compared to a normal adjacent tissue and the expression of miRNAs (miR21, miR146a, miR135a, miR147b and miR155) that regulate immunity genes especially the cytokines of the TH17 pathway. This research has shown that microRNAs 21, 135a and 146a are associated with colorectal cancer. Indeed, these three miRs are overexpressed in cancer tissue compared to healthy tissue. These results clearly confirm the involvement of epigenetics in colorectal cancer. In other words, this study reveals the importance of immunity and specifically the TH17 pathway in the development and presentation of colorectal cancer. These results suggest that TLR4, IL17A, IL17F and IL23R polymorphisms as well as the expression of microRNAs that regulate inflammation and the TH17 pathway are associated with the evolution and progression of the colorectal tumor that could be considered as biomarkers in colorectal cancer.
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Affiliation(s)
- Inés Omrane
- Laboratoire de Génétique Immunologie et Pathologie Humaine, Faculté des Sciences de Tunis, Université de Tunis EL MANAR, Tunisia.
| | - Amel Benammar-Elgaaied
- Laboratoire de Génétique Immunologie et Pathologie Humaine, Faculté des Sciences de Tunis, Université de Tunis EL MANAR, Tunisia
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Wang Z, Cai Q, Jiang Z, Liu B, Zhu Z, Li C. Prognostic role of microRNA-21 in gastric cancer: a meta-analysis. Med Sci Monit 2014; 20:1668-74. [PMID: 25230738 PMCID: PMC4179621 DOI: 10.12659/msm.892096] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Mounting evidence shows that microRNAs may be useful as prognostic biomarkers of gastric cancer. The aim of this meta-analysis was to summarize the predictive role of miR-21 for survival in patients with gastric cancer and to verify the association between expression of miR-21 and clinical characteristics. Material/Methods All the eligible studies were searched by PubMed and EMBASE and clinical characteristics and survival results were extracted. Then a meta-analysis was carried out to clarify the prognostic role of the miR-21 expression in different subgroups. Results We included 8 studies dealing with gastric cancer in this meta-analysis. For overall survival, the pooled hazard ratio of higher miR-21 expression in tumor tissue was 2.00 (95% CI: 1.39–2.88, P<0.01), which could significantly predict poorer survival in gastric cancer patients. Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with tumor differentiation 0.42 (95% CI: 0.25–0.70 p<0.01), lymph node metastasis 6.39(95% CI: 3.11–13.14, P<0.01), and TNM stage 0.38 (95% CI: 0.21–0.67, P<0.01). Conclusions This meta-analysis indicates that miR-21 detection has a prognostic value in patients with gastric cancer. In addition, overexpression of miR-21 is associated with worse tumor differentiation, lymph node metastasis, and TNM stage.
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Affiliation(s)
- Zhenqiang Wang
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
| | - Qiang Cai
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
| | - Zhaoyan Jiang
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
| | - Bingya Liu
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
| | - Zhenggang Zhu
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
| | - Chen Li
- Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (mainland)
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Liu HS, Xiao HS. MicroRNAs as potential biomarkers for gastric cancer. World J Gastroenterol 2014; 20:12007-12017. [PMID: 25232237 PMCID: PMC4161788 DOI: 10.3748/wjg.v20.i34.12007] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 05/06/2014] [Accepted: 06/13/2014] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.
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Zhou X, Wang X, Huang Z, Wang J, Zhu W, Shu Y, Liu P. Prognostic value of miR-21 in various cancers: an updating meta-analysis. PLoS One 2014; 9:e102413. [PMID: 25019505 PMCID: PMC4097394 DOI: 10.1371/journal.pone.0102413] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 06/17/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. METHODS We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). RESULTS The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66-2.19) for OS, 1.42 (95% CI: 1.16-1.74) for DFS and 2.2 (95% CI: 1.64-2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18-4.9) for OS. CONCLUSIONS Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical.
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Affiliation(s)
- Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaping Wang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Zebo Huang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Wang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Zhu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- * E-mail: (PL); (WZ)
| | - Yongqian Shu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Cancer Center of Nanjing Medical University, Nanjing, China
| | - Ping Liu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Cancer Center of Nanjing Medical University, Nanjing, China
- * E-mail: (PL); (WZ)
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Zeng T, Li G. MicroRNA‑10a enhances the metastatic potential of cervical cancer cells by targeting phosphatase and tensin homologue. Mol Med Rep 2014; 10:1377-82. [PMID: 25018014 DOI: 10.3892/mmr.2014.2370] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Accepted: 04/24/2014] [Indexed: 11/05/2022] Open
Abstract
Cervical cancer is one of the leading causes of cancer‑related mortality worldwide. Previously, the upregulation of microRNA (miR)‑10a has been identified in human cervical cancer. The present study firstly demonstrated that miR‑10a was markedly upregulated in primary tumor tissues in patients with positive lymph node metastasis (LN+) compared with negative (LN‑) by quantitative polymerase chain reaction. miR‑10a mimics markedly enhanced cervical cancer cell migration and invasion abilities, and accordingly the miR‑10a inhibitor suppressed those functions. Furthermore, these data suggested that the phosphatase and tensin homologue (PTEN) was inhibited by miR‑10a through an miR‑10a binding site within the 3'‑untranslated region of PTEN at the posttranscriptional level, and that miR‑10a mimics promoted nuclear translocation of β‑catenin. Therefore, it was concluded that the overexpression of miR‑10a contributes to metastasis in cervical cancer by targeting PTEN. miR‑10a may therefore be used clinically as a molecular marker for patients with cervical cancer lymph node metastasis.
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Affiliation(s)
- Tianhe Zeng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China
| | - Guiling Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China
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MicroRNAs 146a and 147b biomarkers for colorectal tumor's localization. BIOMED RESEARCH INTERNATIONAL 2014; 2014:584852. [PMID: 24800242 PMCID: PMC3985145 DOI: 10.1155/2014/584852] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2014] [Revised: 02/11/2014] [Accepted: 02/27/2014] [Indexed: 12/18/2022]
Abstract
The recently identified class of microRNAs (miRs) provided a new insight into cancer research, since abnormalities of members of microRNAs family have been found in various types of cancer. However, the relationship between five miRNAs (miR146a, miR155, miR21, miR135a, and miR147b) and colorectal cancer remains unclear. In the present study, we examined expression of these miRNAs in 25 pair-matched colon cancer tissues and normal colon mucosa. The expression levels of miR146a, miR155, miR21, miR135a, and miR147b were quantified by real-time PCR. We found that miR21, miR146a, and miR135a were all expressed at higher levels in colon tumors. On the other hand, miR146a and miR147b expressions are significantly higher in left colon compared to right colon. These two miRs, especially miR146a, seemed to be markers for the left colon tumors. Moreover, significant proportional and inverse correlations were found between miR expressions in tumor and healthy tissue, and the correlations profiles were different depending on cancer localization. Taken together, these results lead us to suggest the presence of different mechanisms regulating miRs expression and consequently their target genes in left and right colon. So the pathway of colorectal carcinogenesis would be different according to the site of the tumor.
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Bouyssou JMC, Manier S, Huynh D, Issa S, Roccaro AM, Ghobrial IM. Regulation of microRNAs in cancer metastasis. Biochim Biophys Acta Rev Cancer 2014; 1845:255-65. [PMID: 24569228 DOI: 10.1016/j.bbcan.2014.02.002] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2013] [Revised: 01/15/2014] [Accepted: 02/12/2014] [Indexed: 12/13/2022]
Abstract
Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind to specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process.
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Affiliation(s)
- Juliette M C Bouyssou
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, 450 Brookline Avenue, HIM 246, Boston, MA 02215, USA; Ecole de Biologie Industrielle, 32 Boulevard du port, 95094 Cergy-Pontoise cedex, France
| | - Salomon Manier
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, 450 Brookline Avenue, HIM 246, Boston, MA 02215, USA
| | - Daisy Huynh
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, 450 Brookline Avenue, HIM 246, Boston, MA 02215, USA
| | - Samar Issa
- Ecole de Biologie Industrielle, 32 Boulevard du port, 95094 Cergy-Pontoise cedex, France
| | - Aldo M Roccaro
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, 450 Brookline Avenue, HIM 246, Boston, MA 02215, USA
| | - Irene M Ghobrial
- Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, 450 Brookline Avenue, HIM 246, Boston, MA 02215, USA.
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Abstract
Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.
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Wang Z, Wang J, Yang Y, Hao B, Wang R, Li Y, Wu Q. Loss of has-miR-337-3p expression is associated with lymph node metastasis of human gastric cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2013; 32:76. [PMID: 24422944 PMCID: PMC3854519 DOI: 10.1186/1756-9966-32-76] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 10/02/2013] [Indexed: 12/16/2022]
Abstract
Background Metastasis is the major cause of cancer-related death in patients with gastric cancer, and aberrant expression of various microRNAs (miRNAs) is associated with cancer metastasis. Methods Profiling of differentially expressed miRNAs was performed in three cases of primary gastric cancer and the corresponding metastatic lymph node tissues. Then, the five most altered miRNAs were further verified in 16 paired samples. Two of these five miRNAs were further assessed for their effects on the regulation of gastric cancer cell growth and invasion. Results The miRNA profile data showed 151 upregulated miRNAs (≥ 1.5-fold) and 285 downregulated miRNAs (≤ 0.67-fold) in the metastatic tissues compared to the primary gastric cancer tissues. Among these five miRNAs (i.e., hsa-miR-508-5p, hsa-miR-30c, hsa-miR-337-3p, hsa-miR-483-5p, and hsa-miR-134), expression of hsa-miR-337-3p and hsa-miR-134 was significantly downregulated in these 16 lymph node metastatic tissues compared to their primary tumor tissues (P<0.05) and in nine gastric cancer cell lines compared to the nonmalignant GES cell line. Furthermore, induction of hsa-miR-134 or hsa-miR-337-3p expression did not dramatically affect gastric cancer cell proliferation, but transfection of the hsa-miR-337-3p mimic did reduce gastric cancer cell invasion capacity. Conclusions These findings indicate that hsa-miR-337-3p plays a role in the reduction of gastric cancer cell invasion capacity, and further studies on the mechanism of hsa-miR-337-3p in gastric cancer metastasis are warranted.
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Wang JL, Hu Y, Kong X, Wang ZH, Chen HY, Xu J, Fang JY. Candidate microRNA biomarkers in human gastric cancer: a systematic review and validation study. PLoS One 2013; 8:e73683. [PMID: 24040025 PMCID: PMC3767766 DOI: 10.1371/journal.pone.0073683] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 07/19/2013] [Indexed: 12/19/2022] Open
Abstract
Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide and there is therefore a clear need to search for more sensitive early diagnostic biomarkers. We performed a systematic review of eight published miRNA profiling studies that compared GC tissues with adjacent noncancerous tissues. A miRNA ranking system was used that took the frequency of comparisons, direction of differential expression and total sample size into consideration. We identified five miRNAs that were most consistently reported to be upregulated (miR-21, miR-106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR-378 and miR-638). Six of these were further validated in 32 paired sets of GC and adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR-17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the expression of miR-378 was decreased. Moreover, we found a significant association between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and clinicopathological features of GC. These miRNAs may be used for diagnostic and/or prognostic biomarkers for GC and therefore warrant further investigation.
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Affiliation(s)
- Ji-Lin Wang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
| | - Ye Hu
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
| | - Xuan Kong
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
| | - Zhen-Hua Wang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
| | - Hao-Yan Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
| | - Jie Xu
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
- * E-mail: (JX); (JF)
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institution of Digestive Disease, Shanghai, China
- Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China
- State Key Laboratory of Oncogene and Related Genes, Shanghai, China
- * E-mail: (JX); (JF)
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Xu X, Yang X, Xing C, Zhang S, Cao J. miRNA: The nemesis of gastric cancer (Review). Oncol Lett 2013; 6:631-641. [PMID: 24137382 PMCID: PMC3789097 DOI: 10.3892/ol.2013.1428] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 06/13/2013] [Indexed: 12/31/2022] Open
Abstract
microRNAs (miRNAs) are a group of small non-coding RNAs that are ~22 (18 to 25) nucleotides (nt) long and have been associated with a variety of diseases, including cancer. Increasing evidence indicates that miRNAs are essential in the development, diagnosis, treatment and prognosis of a variety of tumors. The utility of miRNAs as biomarkers for diagnosis and of target molecules for the treatment of cancers is increasingly being recognized. With the discovery of circulating miRNAs, a non-invasive approach for the diagnosis and treatment of cancer has been identified. This review summarizes the role of miRNAs in the development of different tumors, as well as a variety of other biological events. Moreover, this review focuses on analyzing the function and mechanism of gastric cancer-related miRNAs and investigates the importance of circulating miRNAs in gastric cancer, as well as their origin. Finally, this review lists a number of the problems that must be solved prior to miRNAs being used as reliable non-invasive tools for the diagnosis, treatment and prognosis of gastric cancer.
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Affiliation(s)
- Xiaohui Xu
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, P.R. China
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Huang Y, Yang YB, Zhang XH, Yu XL, Wang ZB, Cheng XC. MicroRNA-21 gene and cancer. Med Oncol 2013; 30:376. [PMID: 23277281 DOI: 10.1007/s12032-012-0376-8] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 09/14/2012] [Indexed: 12/20/2022]
Abstract
MicroRNAs (miRNAs) are a class of 18-27-nucleotides single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. It has been demonstrated that miRNAs regulate a variety of physiological functions, including development, cell differentiation, proliferation, and apoptosis. There are growing evidence showed that miRNAs can affect the genesis and development of tumor and play a kind of tumor suppressor or oncogenic function by regulating its targetted gene-related signal pathway. miRNA-21 is one of the early discovered miRNAs in human cells, and the expression of miRNA-21 is significantly upregulated in different kinds of solid tumors. Its abnormal expression levels are closely associated with pathogenesis of cancers. This review summarizes the recent study on the field of miRNA-21 and its association with cancer.
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Affiliation(s)
- Yong Huang
- Animal Science and Technology College, He Nan University of Science and Technology, Luoyang City 471003, Henan Province, People's Republic of China.
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Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol 2012; 6:620-36. [PMID: 23141800 PMCID: PMC5528346 DOI: 10.1016/j.molonc.2012.10.006] [Citation(s) in RCA: 120] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Accepted: 10/17/2012] [Indexed: 02/07/2023] Open
Abstract
Current hypotheses suggest that tumors originate from cells that carry out a process of "malignant reprogramming" driven by genetic and epigenetic alterations. Multiples studies reported the existence of stem-cell-like cells that acquire the ability to self-renew and are able to generate the bulk of more differentiated cells that form the tumor. This population of cancer cells, called cancer stem cells (CSC), is responsible for sustaining the tumor growth and, under determined conditions, can disseminate and migrate to give rise to secondary tumors or metastases to distant organs. Furthermore, CSCs have shown to be more resistant to anti-tumor treatments than the non-stem cancer cells, suggesting that surviving CSCs could be responsible for tumor relapse after therapy. These important properties have raised the interest in understanding the mechanisms that govern the generation and maintenance of this special population of cells, considered to lie behind the on/off switches of gene expression patterns. In this review, we summarize the most relevant epigenetic alterations, from DNA methylation and histone modifications to the recently discovered miRNAs that contribute to the regulation of cancer stem cell features in tumor progression, metastasis and response to chemotherapy.
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Affiliation(s)
- Purificación Muñoz
- Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain
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Abstract
Considering the high mortality rates and the unfavorable prognosis of gastric cancer (GC) as well as the lack of a clinical predictive marker, which is sufficiently sensitive to GC, it is of great significance to investigate new sensitive and specific markers for GC diagnosis. MicroRNAs (miRNAs) could be a practical form of potential biomarkers in the diagnosis of human disease, and they are confirmed to be closely associated with GC. In this review, we discuss the recent research results that indicate the feasibility and clinical applications of miRNAs in GC. Although several challenges remain to be addressed, miRNAs have the potential to be applied in the diagnosis of GC.
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