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