HBx Mediated Increase of DDX17 Contributes to HBV-Related Hepatocellular Carcinoma Tumorigenesis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jul 5

PMID 35784274

Authors

Mei-Ling Dong

Xu Wen

Xin He

Ji-Hua Ren

Hai-Bo Yu

Yi-Ping Qin

Zhen Yang

Min-Li Yang

Chong-Yang Zhou

Hui Zhang

Sheng-Tao Cheng

Juan Chen

Affiliations

Soon will be listed here.

Abstract

HBV is strongly associated with HCC development and DEAD-box RNA helicase 17 (DDX17) is a very important member of the DEAD box family that plays key roles in HCC development by promoting cancer metastasis. However, the important role of DDX17 in the pathogenesis of HBV-related HCC remains unclear. In this study, we investigated the role of DDX17 in the replication of HBV and the development of HBV-associated HCC. Based on data from the GEO database and HBV-infected cells, we found that DDX17 was upregulated by the HBV viral protein X (HBx). Mechanistically, increased DDX17 expression promoted HBV replication and transcription by upregulating ZWINT. Further study showed that DDX17 could promote HBx-mediated HCC metastasis. Finally, the promotive effect of DDX17 on HBV and HBV-related HCC was confirmed . In summary, the results revealed the novel role of DDX17 in the replication of HBV and the metastasis of HBV-associated HCC.

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References

Wu K . The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness. Biomed J. 2020; 43(2):107-114. PMC: 7283569. DOI: 10.1016/j.bj.2020.03.001. View

Fuller-Pace F . DEAD box RNA helicase functions in cancer. RNA Biol. 2013; 10(1):121-32. PMC: 3590229. DOI: 10.4161/rna.23312. View

Alvarez E, Demeulemeester J, Otero P, Jolly C, Garcia-Souto D, Pequeno-Valtierra A . Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture. Nat Commun. 2021; 12(1):6910. PMC: 8617174. DOI: 10.1038/s41467-021-26805-8. View

Kailasam Mani S, Yan B, Cui Z, Sun J, Utturkar S, Foca A . Restoration of RNA helicase DDX5 suppresses hepatitis B virus (HBV) biosynthesis and Wnt signaling in HBV-related hepatocellular carcinoma. Theranostics. 2020; 10(24):10957-10972. PMC: 7532671. DOI: 10.7150/thno.49629. View

Liu X, Tang S, Wu S, Luo Y, Cao M, Zhou H . Epigenetic modulation of insulin-like growth factor-II overexpression by hepatitis B virus X protein in hepatocellular carcinoma. Am J Cancer Res. 2015; 5(3):956-78. PMC: 4449429. View

Bayo J, Fiore E, Dominguez L, Real A, Malvicini M, Rizzo M . A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets. J Hepatol. 2019; 71(1):78-90. DOI: 10.1016/j.jhep.2019.03.007. View

Zhang Q, Song G, Yao L, Liu Y, Liu M, Li S . miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3. J Exp Clin Cancer Res. 2018; 37(1):14. PMC: 5789631. DOI: 10.1186/s13046-018-0681-y. View

Xiao Y, Najeeb R, Ma D, Yang K, Zhong Q, Liu Q . Upregulation of CENPM promotes hepatocarcinogenesis through mutiple mechanisms. J Exp Clin Cancer Res. 2019; 38(1):458. PMC: 6839178. DOI: 10.1186/s13046-019-1444-0. View

Zhou H, Li F, Cheng S, Xu Y, Deng H, Gu D . DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis. Hepatology. 2021; 75(4):847-865. PMC: 9304246. DOI: 10.1002/hep.32195. View

10.

Renzulli M, Brandi N, Argalia G, Brocchi S, Farolfi A, Fanti S . Morphological, dynamic and functional characteristics of liver pseudolesions and benign lesions. Radiol Med. 2022; 127(2):129-144. DOI: 10.1007/s11547-022-01449-w. View

11.

Ghavimi S, Apfel T, Azimi H, Persaud A, Pyrsopoulos N . Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options. J Clin Transl Hepatol. 2020; 8(2):168-176. PMC: 7438354. DOI: 10.14218/JCTH.2020.00001. View

12.

Chen Y, Li L, Lan J, Cui Y, Rao X, Zhao J . CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma. Mol Cancer. 2022; 21(1):11. PMC: 8725338. DOI: 10.1186/s12943-021-01466-9. View

13.

Xue Y, Jia X, Li C, Zhang K, Li L, Wu J . DDX17 promotes hepatocellular carcinoma progression via inhibiting Klf4 transcriptional activity. Cell Death Dis. 2019; 10(11):814. PMC: 6814716. DOI: 10.1038/s41419-019-2044-9. View

14.

Pan L, Huang X, Liu Z, Ye Y, Li R, Zhang J . Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression. J Clin Invest. 2021; 131(22). PMC: 8592549. DOI: 10.1172/JCI148130. View

15.

Kao S, Cheng W, Wang Y, Wu H, Yeh H, Chen Y . Regulation of miRNA Biogenesis and Histone Modification by K63-Polyubiquitinated DDX17 Controls Cancer Stem-like Features. Cancer Res. 2019; 79(10):2549-2563. DOI: 10.1158/0008-5472.CAN-18-2376. View

16.

Guiu B, Jouve J, Schmitt A, Minello A, Bonnetain F, Cassinotto C . Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial. J Hepatol. 2018; 68(6):1163-1171. DOI: 10.1016/j.jhep.2018.01.022. View

17.

Zhang H, Zhang Y, Zhu X, Chen C, Zhang C, Xia Y . DEAD Box Protein 5 Inhibits Liver Tumorigenesis by Stimulating Autophagy via Interaction with p62/SQSTM1. Hepatology. 2018; 69(3):1046-1063. PMC: 6411283. DOI: 10.1002/hep.30300. View

18.

Wang P, Guo Q, Wang Z, Qian H . HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway. Mol Cell Biochem. 2012; 372(1-2):161-8. DOI: 10.1007/s11010-012-1457-x. View

19.

Seo W, Gao Y, He Y, Sun J, Xu H, Feng D . ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles. J Hepatol. 2019; 71(5):1000-1011. PMC: 6801025. DOI: 10.1016/j.jhep.2019.06.018. View

20.

De Silva D, Poliquin S, Zeng R, Zamudio-Ochoa A, Marrero N, Perez-Martinez X . The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation. Nucleic Acids Res. 2017; 45(11):6628-6643. PMC: 5499750. DOI: 10.1093/nar/gkx426. View