MiR-31 Functions as an Oncomir Which Promotes Epithelial-Mesenchymal Transition via Regulating BAP1 in Cervical Cancer.

Nan Wang,Yong Li,Jianhong Zhou

doi:10.1155/2017/6361420

Abstract

MicroRNA-31 (miR-31) functions as tumor suppressors or oncogenes that are involved in tumor behavior. However, the function of miR-31 in cervical carcinogenesis remains unclear. The aim of this study was to validate the potential role of miR-31 and BRCA1-associated protein-1 (BAP1) on regulating epithelial-mesenchymal transition (EMT) in cervical cancer. In the present study, qRT-PCR assay revealed that the expression of miR-31 was upregulated in human cervical cancer cells and clinical tissues. Results of wound healing and cell migration assay revealed that knockdown of miR-31 inhibited cell metastasis and migration. Bioinformatic and dual-luciferase reporter gene assay showed that BAP1 was the direct target of miR-31. Furthermore, the results revealed that miR-31 promoted proliferation and EMT in cervical cancer cells and accelerated the development of tumor growth in vivo xenograft experiment by inhibiting BAP1 expression. Overall, these results highlight an important role of miR-31 functioning as an oncomir which could promote EMT in cervical cancer via downregulating BAP1 expression. Thus, downregulation of miR-31 could be a novel approach for the molecular treatment of cervical cancers and other malignancies.

Highlights

Cervical cancer, a common malignancy in gynecology, is the fourth leading cause of cancer-related deaths in female worldwide [1]
The results revealed that miR-31 promoted proliferation and epithelial-mesenchymal transition (EMT) in cervical cancer cells and accelerated the development of tumor growth in vivo xenograft experiment by inhibiting BRCA1associated protein-1 (BAP1) expression
We further examined whether BAP1 was a direct target of miR-31 in cervical cancer cells using dual-luciferase reporter assay

Summary

Introduction

A common malignancy in gynecology, is the fourth leading cause of cancer-related deaths in female worldwide [1]. Recent evidences recognized that aberrant miRNAs expression is associated with cell malignant transformation, especially in tumorigenesis and tumor development [5, 6]. MiR-31 has been reported as upregulated in cervical cancer, which implies that miR-31 may serve as an onco-miRNA participating in the development of cervical cancer [12]. Whether miR-31 can induce EMT or other malignant transformation in cervical cancer remains unknown. There has very little research on the role of BAP1 in cervical cancer and the relationship between miR-31-BAP1 and EMT has not yet been reported. BAP1 was a direct target of miR-31; downregulation of BAP1 by miR-31induced EMT in cervical cancer. Our study clarified previously unidentified prometastatic roles of miR-31 in cervical cancer and miR-31-BAP1 pathway might be a new potential target for therapy in cervical metastasis

Materials and Methods

Results

Findings

Discussion