生物化学与生物物理学报(英文版)2024,Vol.56Issue(1) :114-128.DOI:10.3724/abbs.2023267

Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m6A-dependent miR-17-5p maturation-induced ZBTB4 depletion

Jingyi Ni Xiaoyun Lu Xiangxiang Gao Conghui Jin Junfeng Mao
生物化学与生物物理学报(英文版)2024,Vol.56Issue(1) :114-128.DOI:10.3724/abbs.2023267

Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m6A-dependent miR-17-5p maturation-induced ZBTB4 depletion

Jingyi Ni 1Xiaoyun Lu 2Xiangxiang Gao 1Conghui Jin 1Junfeng Mao3
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作者信息

  • 1. Department of Oncology,Affiliated Tumor Hospital of Nantong University,Nantong 226361,China
  • 2. Department of Pathology,Affiliated Tumor Hospital of Nantong University,Nantong 226361,China
  • 3. Department of Breast Surgery,Affiliated Tumor Hospital of Nantong University,Nantong 226361,China
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Abstract

Triple-negative breast cancer(TNBC)is a subtype of breast cancer,and its mechanisms of occurrence and devel-opment 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,migra-tion,and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m6A-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.

Key words

FTO demethylase/m6A modification/miR-17-5p/ZBTB4/triple-negative breast cancer

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基金项目

Guiding Project of Nantong Health and Health Commission of Jiangsu Province(MSZ2022024)

Special Project of Clinical Medicine of Nantong University of Jiangsu Province(2022JY010)

出版年

2024
生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCDCSCD
影响因子:0.772
ISSN:1672-9145
参考文献量52
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