Multi-omics analysis of lactate metabolism gene regulation in Clonorchis sinensis-associated hepatocellular carcinoma

被引:0
作者
Lin, Qiumei [1 ]
Chen, Junxian [1 ]
Zhou, Lingling [1 ]
Fang, Min [1 ,7 ]
Wei, Caibiao [1 ]
Huang, Taijun [1 ]
Xu, Yulong [1 ]
Gao, Jie [1 ]
Liu, Fengfei [1 ]
Tang, Zeli [5 ,6 ]
Zhu, Jian-Kang [3 ,4 ]
Yang, Weilong [2 ,3 ,4 ]
机构
[1] Guangxi Med Univ Canc Hosp, Dept Clin Lab, Nanning, Peoples R China
[2] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou, Peoples R China
[3] Southern Univ Sci & Technol, Inst Adv Biotechnol, Shenzhen, Peoples R China
[4] Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
[5] Guangxi Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Nanning 530021, Peoples R China
[6] Guangxi Med Univ, Educ Dept Guangxi Zhuang Autonomous Reg, Key Lab Basic Res Reg Dis, Nanning, Peoples R China
[7] Guangxi Med Univ Canc Hosp, Engn Res Ctr Tissue & Organ Injury & Repair Med, Nanning, Peoples R China
基金
美国国家科学基金会;
关键词
<italic>Clonorchis sinensis</italic>; Hepatocellular carcinoma; Lactate metabolism; Multi-omics;
D O I
10.1186/s13071-025-06947-0
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
BackgroundAlthough 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
引用
收藏
页数:12
相关论文
共 66 条
[1]   The lactate receptor GPR81 promotes breast cancer growth via a paracrine mechanism involving antigen-presenting cells in the tumor microenvironment [J].
Brown, Timothy P. ;
Bhattacharjee, Pushpak ;
Ramachandran, Sabarish ;
Sivaprakasam, Sathish ;
Ristic, Bojana ;
Sikder, Mohd Omar F. ;
Ganapathy, Vadivel .
ONCOGENE, 2020, 39 (16) :3292-3304
[2]   Read trimming has minimal effect on bacterial SNP-calling accuracy [J].
Bush, Stephen J. .
MICROBIAL GENOMICS, 2020, 6 (12) :1-13
[3]   Lactate modulation of immune responses in inflammatory versus tumour microenvironments [J].
Certo, Michelangelo ;
Tsai, Chin-Hsien ;
Pucino, Valentina ;
Ho, Ping-Chih ;
Mauro, Claudio .
NATURE REVIEWS IMMUNOLOGY, 2021, 21 (03) :151-161
[4]   NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance [J].
Chen, Hengxing ;
Li, Yun ;
Li, Huafu ;
Chen, Xiancong ;
Fu, Huafeng ;
Mao, Deli ;
Chen, Wei ;
Lan, Linxiang ;
Wang, Chunming ;
Hu, Kaishun ;
Li, Jia ;
Zhu, Chengming ;
Evans, Ian ;
Cheung, Eddie ;
Lu, Daning ;
He, Yulong ;
Behrens, Axel ;
Yin, Dong ;
Zhang, Changhua .
NATURE, 2024, 631 (8021) :663-669
[5]   Aerobic glycolysis enhances HBx-initiated hepatocellular carcinogenesis via NF-κBp65/HK2 signalling [J].
Chen, Lingjun ;
Lin, Xianyi ;
Lei, Yiming ;
Xu, Xuan ;
Zhou, Qi ;
Chen, Yan ;
Liu, Huiling ;
Jiang, Jie ;
Yang, Yidong ;
Zheng, Fengping ;
Wu, Bin .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2022, 41 (01)
[6]   NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development [J].
Chen, Wenbiao ;
Guo, Liliangzi ;
Xu, Huixuan ;
Dai, Yong ;
Yao, Jun ;
Wang, Lisheng .
ONCOGENESIS, 2024, 13 (01)
[7]   WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1 [J].
Chen, Yunhao ;
Peng, Chuanhui ;
Chen, Junru ;
Chen, Diyu ;
Yang, Beng ;
He, Bin ;
Hu, Wendi ;
Zhang, Yanpeng ;
Liu, Hua ;
Dai, Longfei ;
Xie, Haiyang ;
Zhou, Lin ;
Wu, Jian ;
Zheng, Shusen .
MOLECULAR CANCER, 2019, 18 (01)
[8]   The multiple roles of LDH in cancer [J].
Claps, Giuseppina ;
Faouzi, Sara ;
Quidville, Virginie ;
Chehade, Feras ;
Shen, Shensi ;
Vagner, Stephan ;
Robert, Caroline .
NATURE REVIEWS CLINICAL ONCOLOGY, 2022, 19 (12) :749-762
[9]   Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis [J].
Dasgupta, Paramita ;
Henshaw, Chloe ;
Youlden, Danny R. ;
Clark, Paul J. ;
Aitken, Joanne F. ;
Baade, Peter D. .
FRONTIERS IN ONCOLOGY, 2020, 10
[10]   Angiogenesis in Schistosoma haematobium-associated urinary bladder cancer [J].
Dematei, Anderson ;
Fernandes, Ruben ;
Soares, Raquel ;
Alves, Helena ;
Richter, Joachim ;
Botelho, Monica C. .
APMIS, 2017, 125 (12) :1056-1062