Potentials as biomarker and therapeutic target of upregulated long non-coding RNA HLA-F antisense RNA 1 in hepatitis B virus-associated hepatocellular carcinoma

IF 1.9 4区医学 Q3 GENETICS & HEREDITY Virus Genes Pub Date : 2024-04-03 DOI:10.1007/s11262-024-02065-8

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Abstract

The tissue-specific characteristics have encouraged researchers to identify organ-specific lncRNAs as disease biomarkers. This study aimed to identify the clinical and functional roles of long non-coding RNA HLA-F antisense RNA 1 (HLA-F-AS1) in hepatitis B virus (HBV)-hepatocellular carcinoma (HCC). A total of 121 HBV-HCC, 81 chronic hepatitis B (CHB), and 85 normal liver tissues were evaluated in this study. Real-time quantitative PCR assay was used to evaluate the RNA expression levels. Performance in diagnosis was compared between alpha fetoprotein (AFP) and HLA-F-AS1 using Receiver Operating Characteristic (ROC) curves. Performance in post-hepatectomy prognosis with high or low HLA-F-AS1 was compared using Kaplan–Meier curves. Multi-variable analysis was used to determine the informative predictors. Downstream miRNAs for HLA-F-AS1 were predicted and miR-128-3p was confirmed by luciferase reporter assay and RNA pull-down assay. In vitro functional analysis was performed by MTS reagent for cell proliferation and transwell assay for cell migration. HLA-F-AS1 levels were significantly increased in the HBV-HCC compared to normal healthy tissue and CHB tissues. HLA-F-AS1 exhibited a well potential in making a distinction between HBV-HCC and health, as well as HBV-HCC and CHB. The survival analysis revealed that patients with high levels of HLA-F-AS1 tend to shorter overall survival times. The best prognostic performance was achieved by HLA-F-AS1 after multi-variable analysis (HR 2.290, 95% CI 1.191–4.403, p = 0.013). Functional analysis showed that HLA-F-AS1 promoted cell proliferation and migration via miR-128-3p. Up-regulation of HLA-F-AS1 could serve as a promising diagnostic and prognostic marker for HBV-HCC after surgery, maybe useful in the management of HBV-HCC patients. HLA-F-AS1 can promote the progression of HBV-HCC, may be useful in the targeting treatment of HBV-HCC patients.

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乙型肝炎病毒相关肝细胞癌中上调的长非编码 RNA HLA-F 反义 RNA 1 作为生物标记物和治疗靶点的潜力

摘要组织特异性特征促使研究人员将器官特异性lncRNAs鉴定为疾病生物标志物。本研究旨在确定长非编码 RNA HLA-F 反义 RNA 1（HLA-F-AS1）在乙型肝炎病毒（HBV）-肝细胞癌（HCC）中的临床和功能作用。本研究共评估了 121 例 HBV-HCC、81 例慢性乙型肝炎（CHB）和 85 例正常肝组织。研究采用实时定量 PCR 法评估 RNA 表达水平。使用接收者操作特征曲线（ROC）比较了甲胎蛋白（AFP）和 HLA-F-AS1 的诊断效果。使用 Kaplan-Meier 曲线比较了高或低 HLA-F-AS1 对肝切除术后预后的影响。多变量分析用于确定有参考价值的预测因子。HLA-F-AS1的下游miRNA被预测出来，miR-128-3p通过荧光素酶报告实验和RNA牵引实验得到证实。体外功能分析采用 MTS 试剂检测细胞增殖，采用跨孔试验检测细胞迁移。与正常健康组织和 CHB 组织相比，HBV-HCC 中的 HLA-F-AS1 水平明显升高。HLA-F-AS1 在区分 HBV-HCC 和健康组织以及 HBV-HCC 和慢性阻塞性肺病方面具有很好的潜力。生存分析表明，HLA-F-AS1水平高的患者总生存时间往往较短。经过多变量分析，HLA-F-AS1 的预后效果最好（HR 2.290，95% CI 1.191-4.403，p = 0.013）。功能分析显示，HLA-F-AS1通过miR-128-3p促进细胞增殖和迁移。HLA-F-AS1的上调可作为术后HBV-HCC的诊断和预后标志物，或许有助于HBV-HCC患者的治疗。HLA-F-AS1能促进HBV-HCC的进展，可能有助于HBV-HCC患者的靶向治疗。

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来源期刊

Virus Genes 医学-病毒学

CiteScore

3.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Viruses are convenient models for the elucidation of life processes. The study of viruses is again on the cutting edge of biological sciences: systems biology, genomics, proteomics, metagenomics, using the newest most powerful tools. Huge amounts of new details on virus interactions with the cell, other pathogens and the hosts – animal (including human), insect, fungal, plant, bacterial, and archaeal - and their role in infection and disease are forthcoming in perplexing details requiring analysis and comments. Virus Genes is dedicated to the publication of studies on the structure and function of viruses and their genes, the molecular and systems interactions with the host and all applications derived thereof, providing a forum for the analysis of data and discussion of its implications, and the development of new hypotheses.