研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

转录组学特征研究揭示了METTL7A通过p53信号通路和免疫调节通路抑制黑色素瘤的进展。

Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway.

发表日期:2023
作者: Duoli Zhang, Tao Zou, Qingsong Liu, Jie Chen, Mintao Xiao, Anfu Zheng, Zhuo Zhang, Fukuan Du, Yalan Dai, Shixin Xiang, Xu Wu, Mingxing Li, Yu Chen, Yueshui Zhao, Jing Shen, Guiquan Chen, Zhangang Xiao
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

METTL7A 是一个编码蛋白的基因,预计与甲基化相关,并且其表达紊乱与多种疾病相关。然而,鲜有研究探讨 METTL7A 与肿瘤恶性表型以及参与潜在机制之间的关系。我们通过计算机辅助分析和分子生物学技术相结合的方法进行研究,以探索 METTL7A 在癌症进展中的生物学功能。在 TCGA 数据库中提取基因表达和临床信息以探索 METTL7A 的表达变异和预后价值。在体外,进行了 CCK8、转漏、创伤愈合和集落形成实验,以探索 METTL7A 在癌细胞中的生物学功能。进行基因集富集分析 (GSEA) 以探索 METTL7A 参与的信号通路,并通过免疫印迹验证。总之,METTL7A 在大多数癌组织中下调,其低表达与更短的总生存期相关。在黑色素瘤中,METTL7A 的下调与较差的临床分期、较低水平的 TIL 渗入、较高的化疗药物 IC50 水平和较差的免疫治疗结果相关。qPCR 结果证实了 METTL7A 在黑色素瘤细胞中下调的情况。细胞功能实验证明 METTL7A 敲低促进了黑色素瘤细胞的增殖、侵袭、迁移和克隆形成。机制研究表明 METTL7A 通过 p53 信号通路抑制肿瘤发生能力。同时,METTL7A 也是一个潜在的免疫调节因子。©2023 Zhang et al.
METTL7A is a protein-coding gene expected to be associated with methylation, and its expression disorder is associated with a range of diseases. However, few research have been carried out to explore the relationship between METTL7A and tumor malignant phenotype as well as the involvement potential mechanism. We conducted our research via a combination of silico analysis and molecular biology techniques to investigate the biological function of METTL7A in the progression of cancer. Gene expression and clinical information were extracted from the TCGA database to explore expression variation and prognostic value of METTL7A. In vitro, CCK8, transwell, wound healing and colony formation assays were conducted to explore the biological functions of METT7A in cancer cell. GSEA was performed to explore the signaling pathway involved in METTL7A and validated via western blotting. In conclusion, METTL7A was downregulated in most cancer tissues and its low expression was associated with shorter overall survival. In melanoma, METTL7A downregulation was associated with poorer clinical staging, lower levels of TIL infiltration, higher IC50 levels of chemotherapeutic agents, and poorer immunotherapy outcomes. QPCR results confirm that METTL7A is down-regulated in melanoma cells. Cell function assays showed that METTL7A knockdown promoted proliferation, invasion, migration and clone formation of melanoma cells. Mechanistic studies showed that METTL7A inhibits tumorigenicity through the p53 signaling pathway. Meanwhile, METTL7A is also a potential immune regulatory factor.©2023 Zhang et al.