MiR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1

Wen-Ting Wei,Xin-Xin Nian,Shu-Yang Wang,Yong-Xia Wang,Hong-Li Jiao,Zhi-Yuan Xiao,Ya-Ping Ye,Run-Wei Yang,Wen-Ting Liao,Yan-Qing Ding

doi:10.1186/s12935-017-0461-3

Abstract

BackgroundmiRNAs are regarded as molecular biomarkers and therapeutic targets for colorectal cancer (CRC), a series of miRNAs have been proven to involve into CRC carcinogenesis, invasion and metastasis. Aberrant miR-422a expression and its roles have been reported in some cancers. However, the function and underlying mechanism of miR-422a in the progression of CRC remain largely unknown.MethodsReal-time PCR were used to quantify miR-422a expression in CRC tissues. Both vivo and vitro functional assays showed miR-422a inhibits CRC cell proliferation. Target prediction program (miRBase) and luciferase reporter assays were conducted to confirm the target genes AKT1 and MAPK1 of miR-422a. Specimens from 50 patients with CRC were analyzed for the correlation between the expression of miR-422a and the expression of the target genes AKT1 and MAPK1 by real-time PCR.ResultsMiR-422a was down‑regulated in CRC tissues and cell lines. Ectopic expression of miR-422a inhibited cell proliferation and tumor growth ability; inhibition of endogenous miR-422a, by contrast, promoted cell proliferation and tumor growth ability of CRC cells. MiR-422a directly targets 3′-UTR of the AKT1 and MAPK1, down-regulation of miR-422a led to the activation of Raf/MEK/ERK and PI3K/AKT signaling pathways to promote cell proliferation in CRC. In addition, miR-422a expression was negatively correlated with the expressions of AKT1 and MAPK1 in CRC tissues.ConclusionmiR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.

Highlights

MiRNAs are regarded as molecular biomarkers and therapeutic targets for colorectal cancer (CRC), a series of miRNAs have been proven to involve into CRC carcinogenesis, invasion and metastasis
We report that miR-422a is down‐regulated in CRC tissues and cell lines; ectopic expression of miR-422a inhibits cell proliferation and tumor growth ability, inhibition of endogenous miR-422a, by contrast, promotes cell proliferation and tumor growth ability of CRC cells; miR-422a directly targets 3′-untranslated region (UTR) of the AKT serine/threonine kinase 1 (AKT1) and Mitogen-activated protein kinase 1 (MAPK1), down-regulation of miR-422a led to the activation of Raf/MEK/ERK and PI3K/AKT signaling pathways to promote cell proliferation in CRC
The real-time PCR result was consistent with the GEO database analysis. miR-422a expression was down-regulated in 78% (39/50) of the CRC tissue samples examined (N/T > two-fold) compared to their matched adjacent normal tissues (p < 0.001, Fig. 1c)

Summary

Introduction

MiRNAs are regarded as molecular biomarkers and therapeutic targets for colorectal cancer (CRC), a series of miRNAs have been proven to involve into CRC carcinogenesis, invasion and metastasis. Multiple studies have been conducted to investigate the mutation of genes and their products [4,5,6,7], which prove that the aberrant activation of signaling pathways [8,9,10,11] and microsatellite instability (MSI) [7, 11] are involved in oncogenesis and progression of CRC. Raf/MEK/ERK and PI3K/Akt are both signal transduction pathway that regulate intracellular processes in response to extracellular signals. The aberrant activation of Raf/ MEK/ERK and PI3K/Akt signaling pathway is considered to be an essential issue in tumorigenesis and progression of CRC

Methods

Results

Conclusion