肝细胞癌(HCC)是威胁人类性命的恶性肿瘤之一,由于诊断延迟,生存率仍然很低。同时,lncRNAs在肿瘤预后中具有巨大的应用潜力,因此肝细胞癌的相关研究是不可或缺的。
基于EZH2表达式,差异表达的lncRNAsDElncRNAs),miRNA(DEmiRNA),通过使用TCGA数据库在肝细胞癌中鉴定了mRNA(DMRNAs)。生物信息学技术用于确定关键基因在HCC进展中的作用。进行甲基化和免疫浸润分析以探索hub基因的基本功能。最后,我们进行了细胞功能实验,以研究HCC中鉴定的基因与生物学表型之间的关联.
lncRNA-AC079061.1、hsa-miR-765和VIPR1是影响肝细胞癌预后的独立因素。免疫浸润分析显示,lncRNA-AC079061.1可以改变免疫微环境,从而通过调节免疫相关基因(VIPR1)的表达来抑制HCC的发展。甲基化分析表明,VIPR1的表达与HCC的甲基化水平呈负相关。实验结果表明,lncRNA-AC079061.1和VIPR1在肝癌细胞中经常下调,而hsa-miR-765显著上调。此外,lncRNA-AC079061.1/VIPR1轴抑制HCC细胞的增殖和侵袭。
本研究将lncRNA-AC079061.1/VIPR1轴鉴定为抑制肝细胞癌增殖和侵袭的新型生物标志物,影响最终的疾病结果。
Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable.
Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC.
lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells.
The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.