Abstract

BackgroundmicroRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure.MethodsmiR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR.ResultsmiR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation.ConclusionsmiR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC.

Highlights

  • MicroRNAs play essential roles in the development and progression of gastric cancer (GC)

  • We investigated the relevance of miR-874 in GC development and progression, by assessing the effects of miR-874 on GC cell proliferation, as well as the relationship between miR874 and sperm-associated antigen 9 (SPAG9)

  • Results miR-874 is downregulated in GC miR-874 expression levels in 62 matched GC and tumor-adjacent normal tissues were measured with RTqPCR

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Summary

Introduction

MicroRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure. The 5-year survival rate of patients with GC after radical surgery ranges from 30 to 50%; the high malignancy and heterogeneity of GC, as well as its poor differentiation, are primary causes of poor prognosis [2]. Elucidation of molecular mechanisms underlying GC cell proliferation, survival, and MicroRNAs (miRNAs) are 21–25-nucleotide, singlestranded, non-coding RNAs. miRNAs bind to the 3′ untranslated region (3′-UTR) of target genes, which facilitates mRNA degradation or translation suppression. It has become evident that miRNAs play crucial roles in various biological processes, such that they regulate the expression of approximately 30% of all mRNAs expressed in a cell. Numerous miRNAs have been implicated in various human cancers, exerting either tumor suppressor or oncogenic functions [4]. miR-105 [5], miR-664a-3p [6], miR-451a [7], and miR-18b [8] have recently been identified

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