Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance

科研成果详情

题名	Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance
作者	Zhang, Jianping 1; Wang, Zhuo 2; Zhu, Liyuan 1; Wang, Chaoqun3; Huang, Bifei 3; Zhong, Yiming 1; Ying, Pingting 1; Wang, Hanying 2; Li, Qinglin 4; Feng, Lifeng 1; Wang, Xian 2,5; Jin, Hongchuan 1,6
发表日期	2023
发表期刊	AMERICAN JOURNAL OF CANCER RESEARCH 影响因子和分区
语种	英语
原始文献类型	Article ; Journal Article
关键词	Estrogen receptor alpha (ER alpha) nab-paclitaxel Caveolin 1 (CAV1) translation N6-methyladenosine (m6A) miR199a-5p Estrogen receptor α (ERα)
其他关键词	ALBUMIN-BOUND PACLITAXEL ; SOLVENT-BASED PACLITAXEL ; CANCER PROGRESSION ; CHEMOTHERAPY ; COMBINATION ; BIOGENESIS ; EXPRESSION ; MICRORNAS
摘要	Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ER alpha limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ER alpha increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel. Notably, CAV1 expression inversely correlates with ER alpha and relates to improved clinical outcomes from nab-paclitaxel treatment. Importantly, ER alpha stimulates m6A dependent maturation of miR199a-5p, which is elevated in ER+ breast cancer, to inhibit CAV1 translation by antagonizing m6A modification of CAV1 mRNA. Together, our findings reveal a novel role of ER alpha in promoting m6A modification and subsequent maturation of miR199a-5p, which is upregulated in ER+ breast cancer, leading to the suppression of m6A modification of CAV1 and its mRNA translation, thereby contributing to nab-paclitaxel resistance. Thus, combining an ER antagonist with nab-paclitaxel could offer a promising strategy for treating ER+ breast cancer patients.
资助项目	Zhejiang Provincial Natural Science Foundation of China [LD21H160001]; Zhejiang Natural Science Foundation [LD22H160003]; Science and Technology Project of Jinhua, Zhejiang Province [2023-3-030]; Zhejiang Province Medical and Health Science and Technology Program [2020KY597]
出版者	E-CENTURY PUBLISHING CORP
ISSN	2156-6976
卷号	13 期号:12
页数	24
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:001135869900027
收录类别	SCIE ; PUBMED
URL	查看原文
Pubmed记录号	38187046
通讯作者地址	[Wang, Xian]Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Med Oncol, 3 East Qinchun Rd, Hangzhou 310016, Zhejiang, Peoples R China. ; [Jin, Hongchuan]Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Qinchun East Rd, Hangzhou 310016, Zhejiang, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/206894
专题	其他_附属东阳医院（东阳市人民医院）
通讯作者	Wang, Xian; Jin, Hongchuan
作者单位	1.Zhejiang Univ, Sir Run Run Shaw Hosp, Biomed Res Ctr, Sch Med, Hangzhou, Zhejiang, Peoples R China; 2.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Dongyang Hosp, Dept Pathol, Dongyang, Zhejiang, Peoples R China; 4.Univ Chinese Acad Sci, Canc Hosp, Hangzhou, Zhejiang, Peoples R China; 5.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Med Oncol, 3 East Qinchun Rd, Hangzhou 310016, Zhejiang, Peoples R China; 6.Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Qinchun East Rd, Hangzhou 310016, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jianping,Wang, Zhuo,Zhu, Liyuan,et al. Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2023,13(12).
APA	Zhang, Jianping., Wang, Zhuo., Zhu, Liyuan., Wang, Chaoqun., Huang, Bifei., ... & Jin, Hongchuan. (2023). Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance. AMERICAN JOURNAL OF CANCER RESEARCH, 13(12).
MLA	Zhang, Jianping,et al."Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance".AMERICAN JOURNAL OF CANCER RESEARCH 13.12(2023).