Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis.

Abstract

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.

• Authors: Cheng Zhang, Yu Liang, Ming-Hui Ma, Kun-Zhe Wu, Chun-Dong Zhang, Dong-Qiu Dai
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 51 Issue 5 Pg. 2010-2018 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30522118 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• MIRN376C microRNA, human
• MicroRNAs

Topics

• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Disease Progression
• Down-Regulation
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• Stomach Neoplasms (diagnosis, genetics, pathology)