YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation

作者全名：Li, Yuqiang; Guo, Xiong; Liang, Xiaolong; Wang, Ziwei

作者地址：[Li, Yuqiang; Guo, Xiong; Liang, Xiaolong; Wang, Ziwei] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing 400010, Peoples R China; [Li, Yuqiang] Yanan Univ, Dept Gen Surg, Clin Med Coll 3, Xianyang 712000, Shaanxi, 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：FRONTIERS IN BIOSCIENCE-LANDMARK

ESI学科分类：　

WOS号：WOS:001193907900027

JCR分区：Q2

影响因子：3.3

年份：2024

卷号：29

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：YTHDF1; TCF7; gastric cancer; m(6)A modification; proliferation

摘要：Background: N6-methyladenosine (m(6)A) modification is one of the most common RNA modifications in mammals. m(6)A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domaincontaining family protein 1 (YTHDF1), a m(6)A reader, bind to messenger RNAs (mRNAs) containing a m(6)A modification and this enhances its interaction with the ribosome and promotes translation. The function of YTHDF1 in gastric cancer (GC) has been the subject of earlier studies; however, the precise mechanism underlying YTHDF1's role in GC has not been fully elucidated. Methods: The expression of YTHDF1 was evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting. CCK-8, 5-Ethynyl-2 '-deoxyuridine (EdU) and flow cytometry assays were utilized to explore the effect of YTHDF1 on GC cell viability and proliferation. Transcriptome sequencing and RNA immunoprecipitation assays were utilized to explore the underlying mechanisms mediated by YTHDF1. Results: We observed that YTHDF1 is upregulated in GC cancer tissues. Knockdown of YTHDF1 in GC cells significantly inhibited proliferation and promoted apoptosis, suggesting that YTHDF1 increases proliferation and blocks apoptosis in GC cells. Mechanistically, data gathered suggest that YTHDF1 promotes the translation of the transcription factor TCF7 and this results in activation of the WNT signaling axis. Conclusions: We found that YTHDF1 was upregulated in GC and that YTHDF1 could promote GC progression through modulating the translational efficiency of TCF7. Taken together, these findings may provide a novel therapeutic target for GC.

基金机构：National Natural Science Foundation of China [81974385]

基金资助正文：This study was funded by the National Natural Science Foundation of China (81974385).