Abstract

Gastric cancer (GC) is one of the most common malignancies worldwide. Emerging evidence has shown that aberrant expression of microRNAs (miRNAs) plays important roles in cancer progression. However, little is known about the potential role of miR-217 in GC. In this study, we investigated the role of miR-217 on GC cell proliferation and invasion. The expression of miR-217 was down-regulated in GC cells and human GC tissues. Enforced expression of miR-217 inhibited GC cells proliferation and invasion. Moreover, Glypican-5 (GPC5), a new ocncogene, was identified as the potential target of miR-217. In addition, overexpression of miR-217 impaired GPC5-induced promotion of proliferation and invasion in GC cells. In conclusion, these findings revealed that miR-217 functioned as a tumor suppressor and inhibited the proliferation and invasion of GC cells by targeting GPC5, which might consequently serve as a therapeutic target for GC patients.

Highlights

  • Gastric cancer (GC) is the fourth most common human malignancies and the second leading cause of cancer-related deaths worldwide, with estimated one million new cases per year[1,2,3,4]

  • Accumulating evidence has suggested that miRNAs play a crucial role in the pathogenesis of GC through regulating cell proliferation, apoptosis, migration, ads invasion[26,27,28]

  • MiR-217 was frequently downregulated in human GC cell lines and tissues and the lower level of miR-217 was associated with pTNM stage of GC

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Summary

Introduction

Gastric cancer (GC) is the fourth most common human malignancies and the second leading cause of cancer-related deaths worldwide, with estimated one million new cases per year[1,2,3,4]. Deregulation of miRNAs may lead to aberrant gene expression in various diseases including gastric cancer[14,15,16]. The understanding of the role and function of miRNAs in the GC is still in the early stage. The roles of many other aberrantly expressed miRNAs in GC development are still unknown. Downregulation of miR-217 is a frequent event in various cancers, suggesting its important role in tumorigenesis[17,18,19]. The expression of miR-217 was decreased in GC cell lines and tissues. Lower expression of miR-217was associated with pTNM stage. Overexpression of miR-217 suppressed GC cell invasion and proliferation. Luciferase reporter assay and western blot confirmed that miR-217might function as a tumor suppressor in GC by targetingGlypican-5(GPC5)

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