lncRNA-AC079061.1/VIPR1 轴可能抑制肝细胞癌的发展：生物信息学分析和实验验证。
lncRNA-AC079061.1/VIPR1 axis may suppress the development of hepatocellular carcinoma: a bioinformatics analysis and experimental validation.
机构信息
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shanghai Institute of Liver Disease, Shanghai, 200032, China.
出版信息
J Transl Med. 2022 Aug 29;20(1):379. doi: 10.1186/s12967-022-03573-7.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
肝细胞癌（HCC）是威胁人类生命的最恶性肿瘤之一，由于诊断延误，其生存率仍然较低。同时，lncRNAs 在肿瘤预后中有很大的应用潜力，因此肝细胞癌的相关研究是必不可少的。
方法
基于 EZH2 的表达，利用 TCGA 数据库鉴定肝细胞癌中差异表达的 lncRNAs（DElncRNAs）、miRNAs（DEmiRNAs）和 mRNAs（DEmRNAs）。利用生物信息学技术确定关键基因在 HCC 进展中的作用。进行甲基化和免疫浸润分析，以探讨关键基因的潜在功能。最后，进行细胞功能实验，以研究鉴定基因与 HCC 生物学表型之间的关联。
结果
lncRNA-AC079061.1、hsa-miR-765 和 VIPR1 被确定为影响肝细胞癌预后的独立因素。免疫浸润分析表明，lncRNA-AC079061.1 可以通过调节免疫相关基因（VIPR1）的表达来改变免疫微环境，从而抑制 HCC 的发展。甲基化分析表明，VIPR1 的表达与 HCC 中的甲基化水平呈负相关。实验结果表明，lncRNA-AC079061.1 和 VIPR1 在 HCC 细胞中经常下调，而 hsa-miR-765 则显著上调。此外，lncRNA-AC079061.1/VIPR1 轴抑制了 HCC 细胞的增殖和侵袭。
结论
本研究确定了 lncRNA-AC079061.1/VIPR1 轴作为一种新的生物标志物，抑制了肝细胞癌的增殖和侵袭，影响了最终的疾病结局。
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