Department of Rehabilitation Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410001, Hunan Province, China.
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, Hubei Province, China.
Sci Rep. 2023 Jul 3;13(1):10755. doi: 10.1038/s41598-023-37807-5.
Despite the abnormal expression of 18S rRNA m6A methyltransferase METTL5 being reported in some types of human malignancies, but its effect on hepatocellular carcinoma (HCC) remains to be unclear. This study aims to elucidate the influences of METTL5 on the carcinogenesis and progression of HCC. Expressions of METTL5 gene, transcript, protein, and promoter methylation in HCC were examined through multiple databases, c-BioPortal was used to confirm the genomic alterations of METTL5, the biological functions, target networks of kinases and microRNAs of METTL5, and its interactive differential genes were investigated through LinkedOmics. The possible correlation of METTL5 with the tumor-related infiltration of immune cells for HCC were explored comprehensively by using the online tools of TIMER and TISIDB. Expressions of METTL5 gene, mRNA, and protein were considerably overexpressed in HCC samples in comparison with healthy samples. The high methylation of the METTL5 promoter was observed in HCC tissues. Elevated METTL5 expression exhibited unfavorable survival outcomes in HCC patients. METTL5 expression were enriched in the signaling pathways of ribosome and oxidative phosphorylation, mismatch repair, and spliceosome through the involvement of several cancer-related kinases and miRNAs. The METTL5 expression has a positive correlation with the infiltration degree of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Marker genes of tumor immune-infiltrated cells have strong connection with METTL5. Furthermore, the upregulation of METTL5 was strongly correlated with the immune regulation of immunomodulators, chemokines, and chemokine receptors in the immune microenvironment. The oncogenesis and development of HCC are closely related to METTL5 expression, and the overexpression of METTL5 resulted in the poor survival outcome of HCC patients by regulating tumor immune microenvironment.
尽管已有研究报道 18S rRNA m6A 甲基转移酶 METTL5 在某些人类恶性肿瘤中异常表达，但它对肝细胞癌（HCC）的影响尚不清楚。本研究旨在阐明 METTL5 对 HCC 发生和发展的影响。通过多个数据库检测 HCC 中 METTL5 基因、转录本、蛋白和启动子甲基化的表达，使用 c-BioPortal 确认 METTL5 的基因组改变，通过 LinkedOmics 研究 METTL5 的生物学功能、激酶和 microRNA 靶标网络及其交互差异基因。通过在线工具 TIMER 和 TISIDB 全面探讨 METTL5 与 HCC 肿瘤相关免疫细胞浸润的可能相关性。与健康样本相比，HCC 样本中 METTL5 基因、mRNA 和蛋白的表达明显上调。在 HCC 组织中观察到 METTL5 启动子的高甲基化。升高的 METTL5 表达与 HCC 患者不良的生存结局相关。通过涉及几种癌症相关激酶和 miRNA，METTL5 表达富集在核糖体和氧化磷酸化、错配修复和剪接体信号通路中。METTL5 表达与 HCC 中 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润程度呈正相关。肿瘤免疫浸润细胞的标志物基因与 METTL5 有很强的联系。此外，METTL5 的上调与免疫微环境中免疫调节剂、趋化因子和趋化因子受体的免疫调节密切相关。HCC 的发生发展与 METTL5 的表达密切相关，METTL5 的过表达通过调节肿瘤免疫微环境导致 HCC 患者的生存结局较差。
