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

Haiyan Zhang,Zhiwei Zheng,Lingyun Li,Congcong Wang,Tiantian Gao,Cuicui Yuan

doi:10.1186/s12957-020-01846-3

Abstract

BackgroundMounting 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.MethodsQuantitative 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.ResultsThe 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.ConclusionsCorrectively, 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.

Highlights

Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC)
MiR-489 was downregulated in GC tissues and cell lines RT-PCR was applied for measuring miR-489 expression in 52 paired GC tissues and cell lines
Our results show that miR-489 level is reduced in all two GC cell lines compared with that in GES-1 cells (Fig. 1b)

Summary

Introduction

Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC). By targeting mRNA, multiple signaling pathways could be modulated by miRNAs, thereby participating in various cellular activities, Zhang et al World Journal of Surgical Oncology (2020) 18:73 including cell survival, differentiation, metastasis, and apoptosis [6, 7]. Growing evidences showed that miRNAs were involved in GC development as tumor suppressors or oncogenes. MiR-567 was downregulated in GC tissues and cell lines, miR-567 overexpression inhibited GC tumor growth through PIK3AP1-PI3K/AKT signaling pathway [8]. Downregulation of miR-21 inhibited the growth and metastasis of GC cells, which may be a promotion effect on GC progression [10]. Zhang B et al displayed that miR489 functions as a tumor suppressor in GC tumor growth and invasion [14]. MiR-489’ mechanism in the modulation of GC viability, migration, and invasion needs further investigation

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