Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m 6A-dependent miR-17-5p maturation-induced ZBTB4 depletion

去甲基化酶FTO通过阻断m6A依赖的miR-17-5p成熟诱导的ZBTB4耗竭抑制三阴性乳腺癌的发生发展

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作者:Jingyi Ni, Xiaoyun Lu, Xiangxiang Gao, Conghui Jin, Junfeng Mao

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim 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 identify 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 screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate 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 6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. Our 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.

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