MiR-296 inhibits the metastasis and epithelial-mesenchymal transition of colorectal cancer by targeting S100A4

Zheng He,Qi Li,Mingzhen Li,Junbo Li,Yi Sun,Chengbin Wang,Shiyi Luo,Lianhua Yu

doi:10.1186/s12885-017-3121-z

Abstract

BackgroundDysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers. However, the status of miR-296 and its function in CRC remain unknown.MethodsThe expression of miR-296 was confirmed by qRT-PCR in CRC tissues and cells, and its level was altered by corresponding miRNA vectors. Wound healing and Transwall assays were performed to detect the migration and invasion of CRC cells. The levels of proteins were measured using immunoblotting, immunohistochemistry and immunofluorescence.ResultsUnderexpression of miR-296 was disclosed in CRC tissues and cells. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of CRC patients. In vitro experiments indicated that miR-296 inhibited CRC cell migration and invasion. Mechanically, miR-296 inhibited the epithelial-mesenchymal transition (EMT) of CRC cells. A negative correlation between miR-296 and S100A4 expression was observed in CRC tissues. Luciferase reporter assays indicated that miR-296 inversely regulated the luciferase activity of 3’-UTR of S100A4. Herein, S100A4 was found to be a downstream molecule of miR-296 in CRC. Furthermore, S100A4 mediated the anti-metastatic effects of miR-296 on EMT, migration and invasion of CRC cells.ConclusionsmiR-296 functions as an anti-metastatic factor mainly by suppressing S100A4 in CRC. It potentially acts as a prognostic predictor and a drug-target for CRC patients.

Highlights

Dysregulation of microRNAs is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers
Results miR-296 expression is decreased in CRC To examine the status of miR-296 in CRC, Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on 90 CRC cases
Underexpression of miR-296 correlates with adverse clinical parameters and poor prognosis of CRC patients To clarify the clinical value of miR-296 in CRC, all patients were grouped into miR-296 low and high expression groups according to the median expression of miR-296

Summary

Introduction

Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers. Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). It is of great significance to understand the microRNAs (miRNAs) inhibit the expression of target genes by contributing to the degradation or translational inhibition of target mRNAs [4]. They have been found to be actively involved in different cellular processes [5, 6] including cell proliferation, apoptosis, differentiation and movement. Investigating the expression and biological function of miRNAs in CRC will contribute to the discovery of new biomarkers and drug-targets for CRC patients

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