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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Experimental & Clinical Cancer Research 1/2017

MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2017
Autoren:
Lei Ding, Shanyong Zhang, Mu Xu, Renwen Zhang, Pengcheng Sui, Qing Yang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13046-017-0516-2) contains supplementary material, which is available to authorized users.

Abstract

Background

Accumulating evidence indicates that microRNA-27a (miR-27a) is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-27a in gastric cancer remain unclear.

Methods

Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-27a and its target gene. The function of miR-27a in gastric cancer was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry assay, wound healing assay, migration and invasion assay, immunohistochemistry (IHC), immunofluorescence (IF) and Western blot). A luciferase reporter assay was conducted to confirm the target gene of miR-27a.

Results

We found that miR-27a was commonly overexpressed in gastric cancer and high expression of miR-27a was associated with distant metastasis, lymph node metastasis, advanced T stage and advanced clinical stage. Functional assays demonstrated that overexpression of miR-27a in AGS cells accelerated cell proliferation, migration and invasion and suppressed apoptosis. Meanwhile, opposite results were observed in SGC-7901 cells when miR-27a was suppressed. Consistently, down-regulation of miR-27a inhibited the growth and metastasis of engrafted tumors in vivo. Furthermore, we found PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) to be a new target of miR-27a, and downregulation of PHLPP2 could rescue the effect of anti-miR-27a in gastric cancer cells. In addition, miR-27a-mediated suppression of PHLPP2 led to stimulation of the AKT/GSK3β pathway.

Conclusions

Our data suggest that miR-27a functions as a crucial oncogenic miRNA in gastric cancer. It can promote proliferation and metastasis of tumor cells by suppressing PHLPP2 and activating the AKT/GSK3β pathway. Therefore, miR-27a is a potential novel therapeutic target in gastric cancer treatment.
Zusatzmaterial
Additional file 1: Figure S1. Morphological changes of AGS cells induced by miR-27a Overexpression. Figure S2. Associations between PHLPP2 expression and clinicopathological features. Figure S3. Relative PHLPP2 mRNA expression level in SGC-7901 cells co-transfected with miR-27a antagomir and PHLPP2 siRNA. Figure S4. Relative expression of miR-27a in subcutaneously trans-planted tumor tissues. (DOCX 8407 kb)
13046_2017_516_MOESM1_ESM.docx
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