鉴定一种新型lncRNA预后特征和功能性lncRNA AC115619.1对肝细胞癌的分析。
Identification of a novel lncRNA prognostic signature and analysis of functional lncRNA AC115619.1 in hepatocellular carcinoma.
发表日期:2023
作者:
Binliang Gan, Youwu He, Yonggang Ma, Linfeng Mao, Chuanjie Liao, Ganlu Deng
来源:
Frontiers in Pharmacology
摘要:
背景:肝细胞癌(HCC)是最致命的恶性肿瘤。长链非编码RNA(lncRNA)参与了多种人类恶性肿瘤的发展。本研究旨在建立可靠的标志,并鉴定HCC患者的新生物标志物。方法:从基因表达组(GEO)和癌症基因组图谱(TCGA)数据库中鉴定差异表达的lncRNA(DElncRNAs)。运用单变量、LASSO和多变量Cox回归分析筛选预后lncRNA并建立预后模型。进行受试者工作特征(ROC)曲线和Kaplan-Meier分析以验证该模型的预后价值。通过Spearman分析分析lncRNA与差异m6A基因的关联。应用一系列生物信息学和体外实验来探索关键lncRNA的功能。结果:共鉴定了32个DElncRNAs,其中12个与HCC患者的预后有关。构建了一个由六个预后lncRNA(LINC02428、LINC02163、AC008549.1、AC115619.1、CASC9和LINC02362)组成的预后标志,并且该模型表现出了良好的预后预测能力。此外,还鉴定了12个差异m6A调控因子,并发现RBMX与关键lncRNA AC115619.1呈负相关。AC115619.1在HCC组织中的表达水平较正常组织低,并与临床病理特征、生存率和药物敏感性有显著相关性。AC115619.1的过表达显著抑制了HCC细胞的增殖、迁移和侵袭。结论:本研究为HCC患者提供了一种有前景的预后标志,并鉴定了AC115619.1作为一种新的生物标志物,在调控HCC进展中发挥了重要作用。版权所有 © 2023 Gan, He, Ma, Mao, Liao和Deng.
Background: Hepatocellular carcinoma (HCC) is the deadliest malignancy. Long non-coding RNAs (lncRNAs) are involved in the development of multiple human malignancies. This study aimed to establish a reliable signature and identify novel biomarkers for HCC patients. Methods: Differentially expressed lncRNAs (DElncRNAs) were identified from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate, LASSO, and multivariate Cox regression analyses were applied to screen the prognostic lncRNAs and establish a prognostic model. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were conducted to validate the prognostic value of this model. The association between lncRNAs and differential m6A genes was analyzed by Spearman's analysis. A series of bioinformatic and in vitro experiments were applied to explore the function of hub lncRNA. Results: A total of 32 DElncRNAs were identified, and 12 DElncRNAs were associated with the prognosis of HCC patients. A prognostic signature comprising six prognostic lncRNAs (LINC02428, LINC02163, AC008549.1, AC115619.1, CASC9, and LINC02362) was constructed, and the model exhibited an excellent capacity for prognosis prediction. Furthermore, 12 differential m6A regulators were identified, and RBMX was found to be correlated negatively with the hub lncRNA AC115619.1. The expression level of AC115619.1 was lower in HCC tissues than that in normal tissues and was significantly related to clinicopathologic features, survival rate, and drug sensitivity. Overexpression of AC115619.1 notably inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: This study provided a promising prognostic signature for HCC patients and identified AC115619.1 as a novel biomarker, which plays an essential role in regulating the progression of HCC.Copyright © 2023 Gan, He, Ma, Mao, Liao and Deng.