MiR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway.

Yan Sun,Shaoxuan Wu,Qingxia Fan,Yanyan Chi,Feng Wang,Zhengzheng Shan,Tengfei Zhang,Yana Zhang,Han Xu

doi:10.1111/jcmm.14515

Abstract

miR‐516a‐3p has been reported to play a suppressive role in several types of human tumours. However, the expression level, biological function and fundamental mechanisms of miR‐516a‐3p in breast cancer remain unclear. In the present study, we found that miR‐516a‐3p expression was down‐regulated and Pygopus2 (Pygo2) expression was up‐regulated in human breast cancer tissues and cells. Through analysing the clinicopathological characteristics, we demonstrated that low miR‐516a‐3p expression or positive Pygo2 expression was a predictor of poor prognosis for patients with breast cancer. The results of a dual luciferase reporter assay and Western blot analysis indicated that Pygo2 was a target gene of miR‐516a‐3p. Moreover, overexpression of miR‐516a‐3p inhibited cell growth, migration and invasion as well as epithelial‐mesenchymal transition (EMT) of breast cancer cells, whereas reduced miR‐516a‐3p expression promoted breast cancer cell growth, migration, invasion and EMT. Furthermore, we showed that miR‐516a‐3p suppressed cell proliferation, metastasis and EMT of breast cancer cells by inhibiting Pygo2 expression. We confirmed that miR‐516a‐3p exerted an anti‐tumour effect by inhibiting the activation of the Wnt/β‐catenin pathway. Finally, xenograft tumour models were used to show that miR‐516a‐3p inhibited breast cancer cell growth and EMT via suppressing the Pygo2/Wnt signalling pathway. Taken together, these results show that miR‐516a‐3p inhibits breast cancer cell growth, metastasis and EMT by blocking the Pygo2/ Wnt/β‐catenin pathway.

Highlights

Breast cancer is one of the most common malignancies, ranking second among cancer‐related mortalities in women worldwide[1] and is the most common malignancy in women in China,[2] representing a serious threat to women's health
We demonstrated that miR‐516a‐3p inhibited breast cancer cell growth, metastasis and epithelial‐mesenchymal transition (EMT) by blocking the Pygo2/ Wnt/β‐catenin signalling pathway both in vitro and in vivo
The overall survival (OS) for pa‐ tients with positive Pygo[2] expression was markedly worse than for those patients with negative Pygo[2] expression (P < 0.05, Figure 1G). These results indicate that lower miR‐516a‐3p ex‐ pression or positive Pygo[2] expression is related to poor clinical features in breast cancer patients

Summary

| INTRODUCTION

Breast cancer is one of the most common malignancies, ranking second among cancer‐related mortalities in women worldwide[1] and is the most common malignancy in women in China,[2] representing a serious threat to women's health. A large number of studies have demonstrated that miRNAs can either promote the progression of cancer or act as tumour sup‐ pressors.[6,7] miRNAs play crucial roles in tumour cell migration, invasion and epithelial‐mesenchymal transition (EMT).[8-13]. We investigated the role of miR‐516a‐3p in breast cancer for the first time. Pygo[2] has been shown to promote the proliferation of breast cancer cells.[22]. Zhang S et al[23] reported that Pygo[2] promoted cell invasion and metastasis through decreasing E‐cadherin expression in hepatic carcinoma. The activation of the Wnt/β‐catenin signalling pathway has been reported to accelerate EMT in bladder cancer cells.[26]. We report for the first time the role of miR‐516a‐3p breast cancer. We demonstrated that miR‐516a‐3p inhibited breast cancer cell growth, metastasis and EMT by blocking the Pygo2/ Wnt/β‐catenin signalling pathway both in vitro and in vivo

| MATERIALS AND METHODS

F Control

D Control

Findings

| DISCUSSION