MiR-219-5p targets TBXT and inhibits breast cancer cell EMT and cell migration and invasion

Qin Ye,Shuaishuai Cui,Xing Wang,Mei Yuan,Zhaodi Hu,Dahu Chen,Bibo Li,Conghui Han,Dandan Liu,Yuanyuan Chen

doi:10.1042/bsr20210318

Abstract

miR-219-5p has been reported to act as either a tumor suppressor or a tumor promoter in different cancers by targeting different genes. In the present study, we demonstrated that miR-219-5p negatively regulated the expression of TBXT, a known epithelial–mesenchymal transition (EMT) inducer, by directly binding to TBXT 3′-untranslated region. As a result of its inhibition on TBXT expression, miR-219-5p suppressed EMT and cell migration and invasion in breast cancer cells. The re-introduction of TBXT in miR-219-5p overexpressing cells decreased the inhibitory effects of miR-219 on EMT and cell migration and invasion. Moreover, miR-219-5p decreased breast cancer stem cell (CSC) marker genes expression and reduced the mammosphere forming capability of cells. Overall, our study highlighted that TBXT is a novel target of miR-219-5p. By suppressing TBXT, miR-219-5p plays an important role in EMT and cell migration and invasion of breast cancer cells.

Highlights

Much progress has been made in cancer research, breast cancer remains a major public health concern, as it is the most diagnosed cancer in women worldwide and the second leading cause of cancer-related deaths [1,2]
The deficiency of miR-219-5p has been identified in colon cancer [37], gastric cancer [38], glioblastoma [39] and malignant melanoma [40]. miR-219-5p is up-regulated in hepatocellular carcinoma cells and overexpression of miR-219-5p confers the cells with high metastatic potential [41]. miR-219-5p functions as either an oncogene or a tumor suppressor depending the cellular context and the genes it targets
Our work showed that miR-291-5p can induce the re-appearance of E-cadherin, an epithelial cell marker, in mesenchymal MDA-MB-231 cells, and decrease the expression of N-cadherin and vimentin, two mesenchymal cell markers

Summary

Introduction

Much progress has been made in cancer research, breast cancer remains a major public health concern, as it is the most diagnosed cancer in women worldwide and the second leading cause of cancer-related deaths [1,2]. Breast cancer initiates as a local disease but it often metastasizes to many other important organs, which is the main cause of breast cancer-related deaths [3]. It has been indicated that the epithelial–mesenchymal transition (EMT) is the main mechanism underlying the invasiveness and metastasis of various cancers [4,5]. During the EMT process, epithelial cells lose their cell–cell adhesion feature and cell polarity, and acquire migratory and invasive properties to convert into mesenchymal cells. This transition and new cell characteristics are indispensable for many developmental processes and for the initiation of metastasis of cancer progression. It has been known that transcription factors [6,7], growth factors [8], extracellular ligands [9], epigenetic modulations [10] and microRNAs (miRNAs) [11,12,13,14,15] participate in regulating EMT process

Methods

Results

Conclusion