Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m<sup>6</sup>A-dependent miR-17-5p maturation-induced ZBTB4 depletion
Jingyi Ni, Xiaoyun Lu, Xiangxiang Gao, Conghui Jin, Junfeng Mao
Abstract
<p indent="0mm">Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aimed to investigate the role and molecular mechanisms of the demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identified that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTB domain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screened for relevant miRNAs and mRNAs from the GEO and TCGA databases and found that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrated that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m<sup>6</sup>A-dependent mechanism. Furthermore, we established a xenograft nude mouse model and collected clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. These findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.