Androgen receptor-induced lncRNA SOX2-OT promotes triple-negative breast cancer tumorigenesis via targeting miR-320a-5p/CCR5 axis.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-03-19 DOI:10.1016/j.jbc.2025.108428

Yixuan Hu, Jin Bian, Weiwei Chen, Junfeng Shi, Xiaowei Wei, Yueyao Du, Wenwen Zhang

{"title":"Androgen receptor-induced lncRNA SOX2-OT promotes triple-negative breast cancer tumorigenesis via targeting miR-320a-5p/CCR5 axis.","authors":"Yixuan Hu, Jin Bian, Weiwei Chen, Junfeng Shi, Xiaowei Wei, Yueyao Du, Wenwen Zhang","doi":"10.1016/j.jbc.2025.108428","DOIUrl":null,"url":null,"abstract":"<p><p>Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cells tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of lncRNA expression profiles, we identified an AR-related lncRNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT. Mechanistic analysis demonstrated that SOX2-OT serves as a molecular sponge for miR-320a-5p to regulate the expression of CCR5. In addition, SOX2-OT promotes TNBC cell proliferation and inhibits apoptosis in a miR-320a-5p-dependent manner. Using a xenograft mouse model, we found SOX2-OT/CCR5 axis could promote TNBC tumorigenesis in vivo. Importantly, the AR/SOX2-OT/miR-320a-5p/CCR5 axis is manifested in the tissues of 165 TNBC patients. Collectively, our results suggest that SOX2-OT can regulate AR-induced TNBC tumorigenesis through the miR-320a-5p/CCR5 signaling axis, and reveal the great potential of targeting SOX2-OT for the treatment of TNBC patients.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108428"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jbc.2025.108428","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cells tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of lncRNA expression profiles, we identified an AR-related lncRNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT. Mechanistic analysis demonstrated that SOX2-OT serves as a molecular sponge for miR-320a-5p to regulate the expression of CCR5. In addition, SOX2-OT promotes TNBC cell proliferation and inhibits apoptosis in a miR-320a-5p-dependent manner. Using a xenograft mouse model, we found SOX2-OT/CCR5 axis could promote TNBC tumorigenesis in vivo. Importantly, the AR/SOX2-OT/miR-320a-5p/CCR5 axis is manifested in the tissues of 165 TNBC patients. Collectively, our results suggest that SOX2-OT can regulate AR-induced TNBC tumorigenesis through the miR-320a-5p/CCR5 signaling axis, and reveal the great potential of targeting SOX2-OT for the treatment of TNBC patients.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

期刊介绍： The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.