Deciphering the TCF19/miR-199a-5p/SP1/LOXL2 pathway: Implications for breast cancer metastasis and epithelial-mesenchymal transition
作者全名：Li, Shu-yu; Zhang, Nan; Zhang, Hao; Wang, Ning; Du, Ya-ying; Li, Han-ning; Huang, Chenshen; Li, Xing-rui
作者地址：[Li, Shu-yu; Du, Ya-ying; Li, Han-ning; Li, Xing-rui] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Thyroid & Breast Surg, Wuhan, Peoples R China; [Zhang, Nan] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan, Peoples R China; [Zhang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Wang, Ning] Zhejiang Univ, Huzhou Cent Hosp, Affiliated Hosp, Huzhou, Peoples R China; [Huang, Chenshen] Fujian Med Univ, Fujian Prov Hosp, Dept Endocrinol, Fuzhou, Peoples R China
通信作者：Li, HN; Li, XR (通讯作者)，Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Thyroid & Breast Surg, Wuhan, Peoples R China.; Huang, CS (通讯作者)，Fujian Med Univ, Fujian Prov Hosp, Dept Endocrinol, Fuzhou, Peoples R China.
来源：CANCER LETTERS
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001253255100001
JCR分区：Q1
影响因子：9.1
年份：2024
卷号：597
期号：
开始页：
结束页：
文献类型：Article
关键词：Breast cancer; Epithelial-mesenchymal transition; TCF19/miR-199a-5P/SP1/LOXL2 axis; Metastasis; Computational strategies
摘要：Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro , and promoted the growth and metastatic establishment of xenografts in vivo . TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1 ' s affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.
基金机构：Chongqing Postdoctoral Research Special Funding Project [CSTB2023NSCQBHX0002]; [2023CQBSHTB3095]
基金资助正文：This work was supported by the National Natural Science Foundation of China [Grant Nos. 81802676 and 82303610] ; Wuhan Youth Cadre Project (2017zqnlxr01 and 2017zqnlxr02) ; China Postdoctoral Science Foundation (2023MD734131) ; Chongqing Postdoctoral Sciencer Foundation (CSTB2023NSCQBHX0002) ; Chongqing Postdoctoral Research Special Funding Project (2023CQBSHTB3095) .
