MicroRNA-193a inhibits breast cancer proliferation and metastasis by downregulating WT1.

Feiyan Xie,Shen Zhong,Fen Zhang,Xiaoqu Hu,Yang Jiang,Lili Lin,Sumayyah Hosany,Xiaobo Wang,Shenmeng Gao,Aamir Ahmad

doi:10.1371/journal.pone.0185565

Feiyan Xie, Shen Zhong + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0185565

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Abstract

In many cancers, microRNA-193a (miR-193a) is a suppressor miRNA, but its underlying anti-oncogenic activity in breast cancer is not known. In this study, we found decreased miR-193a (specifically, miR-193a-5p) expression not only in breast cancer cell lines but also in breast cancer tissues as compared with the adjacent non-tumor tissues. Ectopic miR-193a overexpression inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and BT549 cells. miR-193a reduced Wilms’ tumor 1 (WT1) expression and repressed luciferase reporter activity by binding WT1 coding region sequences; mutation of the predicted miR-193a binding site abolished this effect. miR-193a and WT1 expression were significantly inversely correlated in breast cancer tissues. Importantly, the anti-cancer activity induced by miR-193a was partially reversed by WT1 overexpression, indicating an important role for WT1 in such activity related to miR-193a. Our results reveal that miR-193a-WT1 interaction plays an important role in breast cancer metastasis, and suggest that restoring miR-193a expression is a therapeutic strategy in breast cancer.

Highlights

Breast cancer is a clinically heterogeneous disease
We found that miR-193a overexpression inhibited the migration and invasion of breast cancer cells by modulating Wilms’ tumor 1 (WT1) expression
As metastasis was inhibited by miR-193a targeting of WT1 protein, we examined whether WT1 counteracts the anti-metastasis effect induced by miR-193a

Summary

Introduction

Breast cancer is a clinically heterogeneous disease. Aggressive disease is diagnosed in approximately 10–15% of cases, and distant metastases are developed within 3 years of the initial diagnosis. Another typical occurrence is distant metastases that manifest at 10 years or more after the initial diagnosis [1]. Patients face the risk of developing metastasis after initial diagnosis. Defining a cure and assessing metastasis risk factors is difficult, as breast cancer metastasis is of a heterogeneous nature. Research should focus on molecular mechanisms and therapeutic methods against breast carcinogenesis and metastasis that are more precise so that patient survival and quality of life can be improved

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