BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets.MethodsThe METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it.ResultsWe found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC.ConclusionThe m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis.

中文翻译：

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m6A甲基转移酶METTL5促进中性粒细胞胞外陷阱网络释放调节肝细胞癌进展

研究背景肝细胞癌（HCC）是全球最常见的恶性肿瘤之一，由于其高度侵袭性和转移性，预后较差。因此，确定有效的预后标志物和潜在的治疗靶点已得到广泛研究。 METTL5（一种 18S rRNA 甲基转移酶）在 HCC 中异常高。但其在 HCC 中的生物学功能和预后意义在很大程度上仍不清楚。本研究旨在探讨METTL5在HCC进展中的作用，并通过转录组测序阐明其在HCC中可能的分子机制，为鉴定新的HCC预后标志物和治疗靶点提供新的见解。方法利用HCC分析HCC及癌旁组织中METTL5的表达免疫组织化学微阵列和生物信息检索方法将 METTL5 与临床病理特征和生存预后相关联。我们构建了 METTL5 敲低肝细胞癌细胞系模型和动物模型，以确定 METTL5 对肝细胞癌进展的影响。随后进行RNA测序，根据测序结果分析METTL5在HCC中的分子机制，并进行相关实验进行验证。结果我们发现METTL5在肝细胞癌组织中表达升高且与患者不良预后相关，并且在临床病理特征分析显示与TNM分期相关。在敲低 METTL5 的肝癌细胞系中，体外和体内的恶性生物学行为均显着降低。基于测序结果以及GO功能富集分析和KEGG通路富集分析结果，我们发现METTL5可以促进中性粒细胞胞外捕获网络（NETs）的生成和释放，并可能进一步加速HCC的进展。结论m6A甲基转移酶 METTL5 在肝细胞癌 (HCC) 中过度表达，与不良预后相关。 METTL5通过促进中性粒细胞胞外陷阱（NET）网络的产生和释放来加速HCC的恶性进展，为HCC预后中的临床生物标志物和免疫治疗靶点提供新的见解。