MiR-23a Promotes TGF-β1-induced EMT and Tumor Metastasis in Breast Cancer Cells by Directly Targeting CDH1 and Activating Wnt/β-catenin Signaling

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Oct 21

PMID 29050223

Citations 62

Authors

Fei Ma

Wenjie Li

Chunxiao Liu

Wei Li

Haining Yu

Bo Lei

Yanlv Ren

Zhigao Li

Da Pang

Cheng Qian

Affiliations

Soon will be listed here.

Abstract

TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells. We found that miR-23a was upregulated by TGF-β1 post-transcriptionally and Smads directly bound the RNA Smad binding element (R-SBE) of miR-23a. Functional studies showed that inhibition of miR-23a suppressed the TGF-β1-induced EMT, migration, invasion and metastasis of breast cancer both and . In addition, we determined that miR-23a directly targeted and suppressed CDH1, one important gene in EMT phenomenon. Notably, Wnt/β-catenin signaling was activated by the suppression of CDH1 in the miR-23a mediated process of TGF-β1-induced EMT and tumor invasion. These results demonstrate that miR-23a promotes TGF-β1-induced tumor metastasis in breast cancer by targeting CDH1 and activating Wnt/β-catenin signaling. Taken together, our results indicate a novel regulatory mechanism of TGF-β1-induced EMT and suggest that miR-23a might be a potential target in breast cancer therapy.

Citing Articles

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