Analysis of human endogenous retrovirus in hepatocellular carcinomas using HERV-Fcount.

IF 4.2 2区生物学 Q2 MICROBIOLOGY

BMC Microbiology Pub Date : 2025-10-02 DOI:10.1186/s12866-025-04358-w

Ya-Sian Chang, Ming-Hon Hsu, Chin-Chun Chung, I-Lu Lai, Ya-Ting Lee, Ju-Chen Yen, Chieh-Min Chang, Ta-Chih Liu, Jan-Gowth Chang

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引用次数: 0

Abstract

Background: Human endogenous retroviruses (HERVs) are important in the development of human diseases, including cancers, and comprehensive study for hepatocellular carcinoma (HCC) is lacking.

Methods: We analyzed the impacts of HERVs on 254 HCC patients using total RNA sequencing (RNA-seq) and a new approach based on featureCounts (we call it HERV-Fcount), and then evaluated the alterations of HERVs in an HCC cell line after TP53 knockdown and alternative splicing (AS)-related small molecules treatment. We also compared the differences in HERVs detection between the Telescope and HERV-Fcount.

Results: In all, 206 HERVs with differential expression are correlated with patient survival and there are 299 genes located near the 206 survival-related differentially expressed (DE) HERVs. There are 14 HERVs whose expression is in the same direction as their nearby genes and also have survival significance. Among these, 11 are positive regulators, with 7 detected by both methods and 4 unique to HERV-Fcount, and 3 are negative regulators, with 2 detected by both methods and 1 unique to HERV-Fcount. Knockdown of TP53 results in dysregulation of survival-related DE HERVs and their nearby genes. The molecule modulating AS can influence the expressions of HERVs by regulating the host genes near HERVs.

Conclusions: HERV-Fcount detects HERVs faster than the Telescope. In addition to total RNA-seq, which increases the detection of HERVs and their nearby genes, this phenomenon can also be observed with HERV-Fcount. HERVs activation results in dysregulation of nearby genes that could be associated with HCC development and prognosis.

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用HERV-Fcount分析人内源性逆转录病毒在肝细胞癌中的作用。

背景：人内源性逆转录病毒（herv）在包括癌症在内的人类疾病的发展中起着重要作用，目前缺乏对肝细胞癌（HCC）的全面研究。方法：采用总RNA测序（RNA-seq）和基于特征计数的新方法（我们称之为HERV-Fcount）分析了herv对254例HCC患者的影响，然后评估了TP53敲除和选择性剪接（AS）相关小分子治疗后HCC细胞系中herv的变化。我们还比较了望远镜和HERV-Fcount在herv检测上的差异。结果：206例差异表达的herv与患者生存相关，其中299个基因位于206例生存相关差异表达（DE） herv附近。有14种herv的表达方向与其邻近基因相同，也具有生存意义。其中阳性调节因子11个，两种方法均检测到7个，HERV-Fcount唯一的4个；阴性调节因子3个，两种方法均检测到2个，HERV-Fcount唯一的1个。TP53的敲低导致与生存相关的DE herv及其附近基因的失调。调节AS的分子可以通过调控herv附近的宿主基因影响herv的表达。结论：HERV-Fcount检测herv比Telescope更快。除了总RNA-seq增加了对herv及其附近基因的检测外，HERV-Fcount也可以观察到这种现象。herv激活导致附近基因的失调，这可能与HCC的发展和预后有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Microbiology 生物-微生物学

CiteScore

7.20

自引率

0.00%

发文量

280

审稿时长

3 months

期刊介绍： BMC Microbiology is an open access, peer-reviewed journal that considers articles on analytical and functional studies of prokaryotic and eukaryotic microorganisms, viruses and small parasites, as well as host and therapeutic responses to them and their interaction with the environment.