ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1670001
BRMS1L promotes chemotherapy sensitivity by inhibiting autophagy in breast cancer
Provisionally accepted- Jinan University, Guangzhou, China
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Chemoresistance remains a crucial obstacle in breast cancer therapy. The mechanisms underlies chemoresistance need to be deep explored urgently. BRMS1L (Breast cancer metastasis suppressor 1 like), a core component of Sin3A-histone deacetylase (HDAC) co-repressor complex, has been reported to suppress breast cancer metastasis through epigenetically regulating Wnt signal pathway. However, whether BRMS1L could regulate chemosensitivity has not been explored. Herein, we found that higher BRMS1L expression was significantly correlated with increased chemotherapy sensitivity and better prognosis in patients receiving neoadjuvant chemotherapy. In vitro experiments confirmed that chemoresistant breast cancer cells exhibited decreased BRMS1L expression compared to chemosensitive cells. In vivo experiments in nude mice demonstrated that BRMS1L markedly strengthened the chemotherapy effects on xenografts. RNA sequencing (RNA-seq) were performed to elucidate the molecular mechanism underlying BRMS1L-mediated chemosensitivity. Bioinformatic analysis indicated that BRMS1L promotes chemotherapy sensitivity by regulating cellular autophagy. Furthermore, chemoresistant breast cancer cells exhibited elevated autophagy levels and ectopic expression of BRMS1L significantly suppressed protective autopagy through downregulating ATG5. Collectively, these results revealed that BRMS1L enhances chemotherapy sensitivity via inhibiting protevtive autophagy. To our knowledge, this is the first study showed that reduced BRMS1L expression is associated with poor response to neoadjuvant chemotherapy and unfavorable prognosis in breast cancer patients. Our findings uncover a novel role of BRMS1L in chemosensitivity and highlight the potential clinical application of BRMS1L in the treatment of breast cancer.
Keywords: BRMS1L, Atg5, Autophagy, Chemotherapy sensitivity, breast cancer
Received: 21 Jul 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 Qu, Li, Zhang, Zhao, Yang, Wang and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shaohua Qu, qushaohua2009@163.com
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