Increased expression of MUSASHI1 in epithelial breast cancer cells is due to down regulation of miR-125b

Mahboobeh Forouzanfar,Mohammad Hossein Nasr-Esfahani,Kamran Ghaedi,Liana Lachinani,Kianoush Dormiani

doi:10.1186/s12860-021-00348-8

Abstract

BackgroundMusashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression of MSI1 has a role in solid tumor progression. There are different factors that regulate MSI1 expression in various cancer tissues including microRNAs which are considered as one of the most important of these factors. The aim of our study is identification of the molecular cause of maximal expression of MSI1 in epithelial breast cancer cell lines.ResultsAmong predicted microRNAs, miR-125b, miR-637 and miR-802 were able to significantly reduce the luciferase activity. In addition, the relative expression of these three miRNAs were measured in the cancerous cell lines that results showed a significant reduction in expression of all microRNAs. On the other hand, only the overexpression of miR-125b caused a change in the expression pattern of MSI1 in breast epithelial cancer cell lines. Accordingly, our results demonstrated that the exogenous expression of miR-125b decreased not only the MSI1 protein but also expression of epithelial markers in breast cancer cells.ConclusionsThe results of luciferase reporter assay showed that MSI1 is a direct target for miR-125b in epithelial breast cancer cells. Moreover, higher amount of MSI1 in those cell lines seems due to the reduced amount of miR-125b, which is responsible for epithelial features of those kinds of cancer cells. Therefore, the modulation of miR-125b may be a potential approach to help to combat against epithelial breast tumors.

Highlights

Musashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer
Up-regulation of MSI1 was only detected in epithelial breast cancer cell Analysis of transcript and protein of MSI1 were carried out in several breast cancer cell lines with different origins
The results demonstrated that MSI1 was highly expressed in T-47D and MCF-7 cells but not in SKBR3 (HER2-positive cell line) and MBAMD-231 cells (Fig. 1)

Summary

Introduction

Musashi (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression of MSI1 has a role in solid tumor progression. The aim of our study is identification of the molecular cause of maximal expression of MSI1 in epithelial breast cancer cell lines. The expression of MSI1 in HER2-positive breast cancer cell lines is correlated with HER2 and knock down of MSI1 reduces colony expansion of spheroid cultures in tumor cells [14]. MSI protein is essential for the preservation of epithelial property of breast cancer cells whereas overexpression of MSI2 regulates in vivo processing of epithelial-to-mesenchymal transition (EMT). Knocking down of MSI1 or MSI2 in the BT474 cell line enhances mesenchymal markers and decreases epithelial markers expression [15]

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