ORIGINAL RESEARCH article

Front. Oncol.

Sec. Breast Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1593827

Tumor-derived exosomal lncRNA SNHG4 promotes triple-negative breast cancer progression by targeting XPO5

Provisionally accepted
Zhi-Wen  WangZhi-Wen Wang1Hou-Sheng  YangHou-Sheng Yang2Hong-Shan  GuoHong-Shan Guo1Yue-Ying  LiYue-Ying Li3Jin-Yun  ZhongJin-Yun Zhong1Shu  JiangShu Jiang1Jiapeng  LiJiapeng Li1Jun  WangJun Wang1*Zhong-Yi  YangZhong-Yi Yang4*Xing-Hua  LiaoXing-Hua Liao1*
  • 1Wuhan University of Science and Technology, Wuhan, China
  • 2Hunan Normal University, Changsha, Hunan Province, China
  • 3Tianjin Medical University General Hospital, Tianjin, China
  • 4Yueyang People's Hospital, Yueyang, Hunan Province, China

The final, formatted version of the article will be published soon.

Background: Triple-negative breast cancer (TNBC) is the subtype of advanced breast cancer with the shortest survival time and the poorest prognosis, and treatment options are relatively limited.Exosomes, small extracellular vesicles enriched with bioactive molecules, are critical mediators of intercellular communication and have been implicated in cancer progression. The aim of this study was to investigate the molecular mechanism of exosomes promoting the proliferation and migration of TNBC.Methods: In this study, exosomes were identified by Flow cytometry and transmission electron microscopy, and RNA sequencing (RNA-seq) was used to identify differentially expressed genes and downstream regulatory molecules in exosomes. RNA-seq results were supported by bioinformatics analysis and Western blot analysis.. Functional assays including in vivo tumor formation, Colony formation Assay, Scratch migration and transwell assays were performed to study exosomes related phenomena and mechanism.and in vivo. lncRNA SNHG4 was most significantly up-regulated in exosomes, and overexpression of lncRNA SNHG4 significantly promoted the proliferation and migration of TNBC cells. In addition, lncRNA SNHG4 promotes TNBC cell proliferation and migration by upregulating the expression of Exportin 5(XPO5). Silencing XPO5 can effectively attenuate the tumor-promoting effect of serum exosomes in TNBC patients. Mechanistically, lncRNA SNHG4 acts through XPO5-mediated pathways. Silencing XPO5 can effectively inhibit the tumor-promoting effect mediated by lncRNA SNHG4.Taken together, our study revealed that the exosome lncRNA SNHG4 exerts its oncogenic role by activating XPO5-mediated pathways, thereby regulating TNBC cell proliferation and migration. This can be considered as a potential target for TNBC molecular therapy.

Keywords: TNBC, exosome, lncRNA SNHG4, XPO5, proliferation, Migration

Received: 14 Mar 2025; Accepted: 20 May 2025.

Copyright: © 2025 Wang, Yang, Guo, Li, Zhong, Jiang, Li, Wang, Yang and Liao. 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:
Jun Wang, Wuhan University of Science and Technology, Wuhan, China
Zhong-Yi Yang, Yueyang People's Hospital, Yueyang, Hunan Province, China
Xing-Hua Liao, Wuhan University of Science and Technology, Wuhan, China

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