Liao Quan, Xiong Jianping
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Jiangxi Key Laboratory for Individualized Cancer Therapy, Nanchang, Jiangxi 330006, P.R. China.
Exp Ther Med. 2024 Apr 17;27(6):255. doi: 10.3892/etm.2024.12543. eCollection 2024 Jun.
The N-methyladenosine reader YTH N-methyladenosine RNA binding protein 1 (YTHDF1) has been assessed in several tumor types and holds significance in the tumor microenvironment (TME). Furthermore, p53, an important tumor suppressor, is closely associated with the TME. The present study evaluated the roles of YTHDF1 and p53 in regulating the TME in gastric cancer (GC). Genetic alterations in the YTH domain family were analyzed using the cBioPortal database. Expression of YTHDF1 in GC cells and tissues was assessed using the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer data analysis portal and Tumor-Immune System Interactions and Drug Bank (TISIDB) databases, along with reverse-transcription-quantitative PCR and western blotting in GC. The prognostic value of multiple tumors was determined using Kaplan-Meier analysis. Correlation analyses were performed using the TIMER, TISIDB and GEPIA databases. Protein-protein interactions of YTHDF1 were predicted using GeneMANIA and HitPredict, and confirmed using co-immunoprecipitation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the YTHDF1 functional network in GC were performed using LinkedOmics. Genetic alterations revealed that, among the YTH domain family members, YTHDF1 had the highest alteration in GC and was associated with a shorter survival. Additionally, YTHDF1 was significantly negatively associated with the level of CD8 T cells, B cells, macrophages, dendritic cells (DCs) and neutrophils in GC. Furthermore, tumor associate macrophage-related and DC markers were significantly negatively correlated with YTHDF1 expression, whilst regulatory T cells and T cell exhaustion markers were significantly negatively associated with YTHDF1 expression. In addition, compared with that in p53-nonmutant GC cells, YTHDF1 expression was significantly higher in p53-mutated GC cells, indicating a potential association between YTHDF1 and p53. Analyses using the GeneMANIA and HitPredict databases, and co-immunoprecipitation, demonstrated that YTHDF1 interacted with p53. In conclusion, the findings of the present study indicate that YTHDF1 is associated with a poor prognosis and serves an important role in the TME of GC. We hypothesize, for the first time to the best of our knowledge, that YTHDF1 regulates immune cell infiltration by interacting with p53 in GC, which provides a promising direction for future research.
N-甲基腺苷阅读器YTH N-甲基腺苷RNA结合蛋白1（YTHDF1）已在多种肿瘤类型中得到评估，并在肿瘤微环境（TME）中具有重要意义。此外，重要的肿瘤抑制因子p53与TME密切相关。本研究评估了YTHDF1和p53在调节胃癌（GC）TME中的作用。使用cBioPortal数据库分析YTH结构域家族中的基因改变。使用肿瘤免疫评估资源（TIMER）、基因表达谱交互式分析（GEPIA）、阿拉巴马大学伯明翰分校癌症数据分析门户以及肿瘤-免疫系统相互作用和药物库（TISIDB）数据库，以及GC中的逆转录定量PCR和蛋白质印迹法，评估GC细胞和组织中YTHDF1的表达。使用Kaplan-Meier分析确定多种肿瘤的预后价值。使用TIMER、TISIDB和GEPIA数据库进行相关性分析。使用GeneMANIA和HitPredict预测YTHDF1的蛋白质-蛋白质相互作用，并通过免疫共沉淀进行验证。使用LinkedOmics对GC中YTHDF1功能网络进行基因本体论和京都基因与基因组百科全书富集分析。基因改变显示，在YTH结构域家族成员中，YTHDF1在GC中的改变最高，并且与较短的生存期相关。此外，YTHDF1与GC中CD8 T细胞、B细胞、巨噬细胞、树突状细胞（DC）和中性粒细胞的水平显著负相关。此外，肿瘤相关巨噬细胞相关标志物和DC标志物与YTHDF1表达显著负相关，而调节性T细胞和T细胞耗竭标志物与YTHDF1表达显著负相关。此外，与p53非突变GC细胞相比，YTHDF1在p53突变GC细胞中的表达显著更高，表明YTHDF1与p53之间存在潜在关联。使用GeneMANIA和HitPredict数据库以及免疫共沉淀进行的分析表明，YTHDF1与p53相互作用。总之，本研究结果表明，YTHDF1与不良预后相关，并且在GC的TME中起重要作用。据我们所知，我们首次假设YTHDF1通过在GC中与p53相互作用来调节免疫细胞浸润，这为未来的研究提供了一个有前景的方向。
