Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis
Autor: | Ming-Hui Ma, Yu Liang, Kun-Zhe Wu, Cheng Zhang, Chun-Dong Zhang, Dong-Qiu Dai |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Epithelial-Mesenchymal Transition Microarray Physiology Carcinogenesis Down-Regulation Biology medicine.disease_cause lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Stomach Neoplasms Cell Line Tumor microRNA medicine Humans lcsh:QD415-436 Gene Survival analysis lcsh:QP1-981 Cancer MicroRNA Biomarker Middle Aged medicine.disease Prognosis miR-376a Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Disease Progression Biomarker (medicine) Female Gastric cancer |
Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 5, Pp 2010-2018 (2018) |
ISSN: | 1421-9778 |
Popis: | Background/Aims: MicroRNAs have a significant role in the tumorigenesis and progression of cancers, including gastric cancer (GC). Our study aimed to identify a novel biomarker to predict the prognosis of patients with GC. Methods: The GC microarray dataset, GSE28700, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed miRNAs (DEMs). The downregulation of miR-376a expression was verified in GC cell lines and 82 paired GC tissues by performing RT-qPCR and the correlation between its expression and clinicopathological characteristics was also explored. The target genes of miR-376a were predicted using TargetScan7.1, miRDB, and DIANA website tools. A functional enrichment analysis was performed to explore the biological role of the common target genes. Results: Bioinformatics analysis found that miR-376a was downregulated in GC tissues. Compared with the control group, RT-qPCR results showed that the expression of miR-376a in GC cell lines and tissues were also significantly decreased. The expression of miR-376a was statistically associated with T and N stage. Survival analysis with Kaplan–Meier showed that GC patients in the low expression group had a poorer prognosis than those in the high expression group (median survival of 26.4 and 46.9 months, respectively). Univariate and multivariate analysis demonstrated that low miR-376a expression was an independent prognostic marker for poor survival. Functional enrichment analysis indicated that the common targets genes were involved in cell–cell communication, VEGF and mTOR1-mediated signaling, and epithelial-to-mesenchymal transition (EMT). Conclusion: The results suggest that miR-376a could play an important role in the tumorigenesis and progression of GC and act as a novel therapeutic target and prognostic indicator in patients with GC. |
Databáze: | OpenAIRE |
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