FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner

作者全名：Yin, Zhe; Guo, Xiong; Liang, Xiaolong; Wang, Ziwei

作者地址：[Yin, Zhe; Guo, Xiong; Liang, Xiaolong; Wang, Ziwei] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing 400010, Peoples R China; [Yin, Zhe] Chongqing Univ, Chongqing Canc Hosp, Dept Thorac Surg, Canc Hosp, Chongqing 400030, Peoples R China

通信作者：Wang, ZW (通讯作者)，Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing 400010, Peoples R China.

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001205445600001

JCR分区：Q2

影响因子：2.8

年份：2024

卷号：41

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：Gastric cancer; m6A; FTO

摘要：Gastric cancer (GC) is a serious malignant tumour with a high mortality rate and a poor prognosis. Recently, emerging evidence has suggested that N6-methyladenosine (m6A) modification plays a crucial regulatory role in cancer progression. However, the exact role of m6A regulatory factors FTO in GC is unclear. First, the expression of m6A methylation-related regulatory factors in clinical samples and the clinical data of the corresponding patients were obtained from The Cancer Genome Atlas (TCGA-STAD) dataset, and correlation analysis between FTO expression and patient clinicopathological parameters was subsequently performed. qRT-PCR, immunohistochemistry (IHC) and western blotting (WB) were used to verify FTO expression in GC. CCK-8, EdU, flow cytometry and transwell assays were used to evaluate the effect of FTO on the behaviour of GC cells. Transcriptome sequencing and RNA immunoprecipitation analysis were used to explore the potential regulatory mechanisms mediated by FTO. FTO was highly expressed in GC tissues and cells, and high expression of FTO predicted a worse prognosis than low expression. Functionally, overexpression of FTO promoted the proliferation, migration and invasion of GC cells but inhibited cell apoptosis. Mechanistically, we found that FTO is upregulated in GC and promotes GC progression by modulating the expression of MAP4K4. Taken together, our findings provide new insights into the effects of FTO-mediated m6A demethylation and could lead to the development of new strategies for GC monitoring and aggressive treatment.

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available