MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway

Abstract

Background: Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC). The purpose of this study was to explore the biological functions and potential mechanism of miR-489 in GC progression. Methods: Quantitative real-time PCR (qRT-PCR) and western blot were performed to examine the mRNA expression and protein levels of miR-489 and HDAC7. The relationship between miR-489 and HDAC7 was analyzed by Spearman rank correlation. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays were conducted for determining the effect of miR-489 and HDAC7 on GC cell viability, migration, and invasion. TargetScan and luciferase reporter assay were used to confirm the target gene of miR-489 in GC cells. Results: The findings showed that miR-489 was dramatically decreased in GC tissues and GC cell lines (SGC-7901 and MKN45). Moreover, it was closely correlated with overall survival (OS) and progression-free survival (PFS) of GC patients. Downregulation of miR-489 significantly promoted GC cell proliferation, invasion, and migration. Additionally, HDAC7 was confirmed as the direct target of miR-489. Knockdown of HDAC7 exerted inhibited effect on GC progression and it markedly overturned miR-489 inhibitor-medicated effect on GC cells. More interestingly, via targeting HDAC7, miR-489 blocked the activation of PI3K/AKT pathway in GC cells. Conclusions: Correctively, miR-489 played as a tumor suppressor in GC cell growth by targeting HDAC7, and miR-489 might function as a novel biomarker for diagnosis or therapeutic targets of human GC.

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