Estrogen receptor α confers Nab-paclitaxel resistance in breast cancer by promoting miR199a-5p maturation to inhibit Caveolin 1 translation

Author:

Zhang Jianping1,Wang Zuo1,Zhu Liyuan1,Wang Chaoqun2,Zhong Yiming1,Ying Pingting1,Wang Hanying1,Li Qinglin3,Feng Lifeng1,Wang Xian1,Jin Hongchuan1

Affiliation:

1. Sir Run Run Show Hospital of Zhejiang University

2. Dongyang People’s Hospital

3. The Cancer Hospital of the University of Chinese Academy of Sciences

Abstract

Abstract Background Estrogen receptor positive (ER+) breast cancer patients are poorly responsive to Nab-paclitaxel compared to ER negative (ER-) breast cancer patients. Herein, we conducted an investigation regarding the mechanism for ERα confers Nab-paclitaxel resistance in breast cancer.Methods Retrospectively reviewed 116 cases of breast cancer treated with nab-paclitaxel between Jan 2008 and May 2022 in Sir Run Run Shaw Hospital. StataSE 16 software was used to analyze the basic conditions and therapeutic effects. Protein-RNA interactions were validated through RNA immunoprecipitation and RNA pull-down assays. In vitro and in vivo experiments were carried out to testify the effect of ERα on Nab-paclitaxel resistance.Results We show that ERα limits the efficacy of nab-paclitaxel in breast cancer while genetic or pharmacological inhibition of ERα has a synergistic effect with Nab-paclitaxel. Meanwhile, CAV1 expression is negatively correlated to ERα and relevant to the better clinical benefits of Nab-paclitaxel treatment. Importantly, ERα stimulates miR199a-5p maturation to antagonize m6A modification of CAV1 mRNA, thus inhibiting its translation.Conclusions Our results define a novel role of ERα miR199a-5p/CAV1 axis responsible for nab-paclitaxel resistance and propose combining ER antagonist with nab-paclitaxel as a perspective strategy for ER + breast cancer patients.

Publisher

Research Square Platform LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3