MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2

Mei Liu,Yu Chen,Xiaodong Wang,Renyuan Xu,Can Gong

doi:10.1186/s11658-019-0168-7

Abstract

BackgroundChemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells.MethodsThe study used both PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. The expression of miR-5195-3p was determined using quantitative real-time PCR. Cell viability, cell cycle distribution and apoptosis were analyzed using CCK-8 and flow cytometry assays. The target genes of miR-5195-3p were predicted with bioinformatics analysis and confirmed using the luciferase reporter assay.ResultsMiR-5195-3p expression was lower in PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. Upregulation of miR-5195-3p enhanced the sensitivity of PTX-resistant TNBC cells to PTX treatment. EIF4A2 was confirmed as a potential target of miR-5195-3p. EIF4A2 knockdown imitated the effects of miR-5195-3p on chemosensitivity, while restoration of EIF4A2 rescued them.ConclusionThese data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.

Highlights

Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility
MiR-5195-3p was downregulated in PTX-resistant breast cancer tissue and cells To verify the expression level of miR-5195-3p in PTX-resistant breast cancer tissue, quantitative real-time PCR was performed with samples from 36 patients: 18 with PTX-sensitive and 18 with PTX-resistant tumors
We found the miR-5195-3p level was significantly lower in all four breast cancer cell lines (MCF-7, BT549, MDA-MB-468 and MDA-MB-231) than in the normal breast epithelial cell line, MCF-10A

Summary

Introduction

Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells. Accounting for approximately 20% of all cases, triple negative breast cancer (TNBC) is characterized by tumors lacking epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) [2]. Paclitaxel (PTX), a chemotherapeutic agent, is commonly used for tumor therapies, including TNBC, but the increasing development of chemoresistance has negatively impacted its clinical utility for TNBC treatment [5, 6]. There is an urgent need to explore the molecular mechanisms underlying PTC chemoresistance in TNBC.

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Conclusion