华支睾吸虫相关肝癌中乳酸代谢基因调控的多组学分析。

IF 3.5 2区 医学 Q1 PARASITOLOGY
Qiumei Lin, Junxian Chen, Lingling Zhou, Min Fang, Caibiao Wei, Taijun Huang, Yulong Xu, Jie Gao, Fengfei Liu, Zeli Tang, Jian-Kang Zhu, Weilong Yang
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引用次数: 0

摘要

背景:尽管最近的研究强调了乳酸化,一种由乳酸水平升高驱动的翻译后修饰,作为肝细胞癌(HCC)关键细胞通路的关键调节因子,但其对华支睾吸虫(Cs)感染的HCC预后不良的贡献仍然知之甚少。方法:我们首先通过临床回顾性分析发现cs感染HCC患者乳酸代谢酶LDH显著上调。然后,我们进行了多组学分析(RNA-Seq、ATAC-Seq、WGBS-Seq、oxWGBS-Seq和ChIP-Seq),以检测cs感染和cs未感染的HCC肿瘤中392个乳酸代谢相关基因(LMRGs)的差异。使用RT-qPCR进一步验证了6个关键差异表达的LMRGs,以确认它们的表达及其在HCC进展中的潜在作用。结果:鉴定了8个LMRGs的差异表达水平,以及LMRGs启动子中71个可达区域和42个CpG位点。值得注意的是,我们还证明了组蛋白修饰,包括H3K9ac、H3K79me2、H3K4me2、H3K4me3、H3K27ac和H3K4me1,与LMRGs启动子中的染色质可及性有关。最后,TCGA-LIHC队列证实,cs感染和cs未感染的HCC肿瘤中LMRGs的差异表达显著影响HCC的生存结局。结论:我们的研究结果表明,乳酸化在重塑Cs感染期间HCC的特征中起着重要作用,扩大了我们对Cs感染HCC独特特征的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multi-omics analysis of lactate metabolism gene regulation in Clonorchis sinensis-associated hepatocellular carcinoma.

Background: Although recent research has highlighted lactylation, a post-translational modification driven by elevated lactate levels, as a critical regulator of key cellular pathways in hepatocellular carcinoma (HCC), its contribution to the poor prognosis of Clonorchis sinensis (Cs)-infected HCC remains poorly understood.

Methods: We first identified the significant upregulation of the lactate metabolism enzyme LDH in Cs-infected HCC patients through clinical retrospective analysis. We then conducted a multi-omics analysis (RNA-Seq, ATAC-Seq, WGBS-Seq, oxWGBS-Seq, and ChIP-Seq) to examine the differences in 392 lactate metabolism-related genes (LMRGs) between Cs-infected and Cs-noninfected HCC tumors. Six key differentially expressed LMRGs were further validated using RT-qPCR assays to confirm their expression and potential role in HCC progression.

Results: The differential expression levels of 8 LMRGs, along with 71 accessible regions and 42 CpG sites in the promoters of LMRGs, were identified. Notably, we also demonstrated that histone modifications, including H3K9ac, H3K79me2, H3K4me2, H3K4me3, H3K27ac, and H3K4me1, were associated with chromatin accessibility in the promoters of LMRGs. Finally, the TCGA-LIHC cohort confirmed that the differential expression of LMRGs between Cs-infected and Cs-noninfected HCC tumors significantly affects the survival outcomes of HCC.

Conclusions: Our findings revealed that lactylation plays an important role in reshaping the characteristics of HCC during Cs infection, expanding our understanding of the unique features of Cs-infected HCC.

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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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