Reconstruction of the regulatory hypermethylation network controlling hepatocellular carcinoma development during hepatitis C viral infection.

Autor:	Antropova EA; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia., Khlebodarova TM; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia., Demenkov PS; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Volianskaia AR; Novosibirsk State University, Novosibirsk, Russia., Venzel AS; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia., Ivanisenko NV; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia., Gavrilenko AD; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Ivanisenko TV; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia., Adamovskaya AV; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Revva PM; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Kolchanov NA; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Lavrik IN; Translational Inflammation Research, Medical Faculty, Otto von Guericke University Magdeburg, 39106 Magdeburg, Germany., Ivanisenko VA; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia.; Kurchatov Genomic Center of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia.
Jazyk:	angličtina
Zdroj:	Journal of integrative bioinformatics [J Integr Bioinform] 2023 Nov 20; Vol. 20 (3). Date of Electronic Publication: 2023 Nov 20 (Print Publication: 2023).
DOI:	10.1515/jib-2023-0013
Abstrakt:	Hepatocellular carcinoma (HCC) has been associated with hepatitis C viral (HCV) infection as a potential risk factor. Nonetheless, the precise genetic regulatory mechanisms triggered by the virus, leading to virus-induced hepatocarcinogenesis, remain unclear. We hypothesized that HCV proteins might modulate the activity of aberrantly methylated HCC genes through regulatory pathways. Virus-host regulatory pathways, interactions between proteins, gene expression, transport, and stability regulation, were reconstructed using the ANDSystem. Gene expression regulation was statistically significant. Gene network analysis identified four out of 70 HCC marker genes whose expression regulation by viral proteins may be associated with HCC: DNA-binding protein inhibitor ID - 1 (ID1) , flap endonuclease 1 (FEN1) , cyclin-dependent kinase inhibitor 2A (CDKN2A) , and telomerase reverse transcriptase (TERT) . It suggested the following viral protein effects in HCV/human protein heterocomplexes: HCV NS3(p70) protein activates human STAT3 and NOTC1; NS2-3(p23), NS5B(p68), NS1(E2), and core(p21) activate SETD2; NS5A inhibits SMYD3; and NS3 inhibits CCN2. Interestingly, NS3 and E1(gp32) activate c-Jun when it positively regulates CDKN2A and inhibit it when it represses TERT . The discovered regulatory mechanisms might be key areas of focus for creating medications and preventative therapies to decrease the likelihood of HCC development during HCV infection. (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu