Role of miR-653 and miR-29c in downregulation of CYP1A2 expression in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major contributor to the worldwide cancer burden. Recent studies on HCC have demonstrated dramatic alterations in expression of several cytochrome P450 (CYP) family members that play a crucial role in biotransformation of many drugs and other xenobiotics; however,...

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Bibliographic Details
Published in:	Pharmacological reports Vol. 74; no. 1; p. 148
Main Authors:	Krkoška, Martin, Nekvindová, Jana, Nevědělová, Kateřina, Zubáňová, Veronika, Radová, Lenka, Vondráček, Jan, Herůdková, Jarmila, Slabý, Ondřej, Kiss, Igor, Bohovicová, Lucia, Fabian, Pavel, Tylichová, Zuzana, Kala, Zdeněk, Kysela, Petr, Ostřížková, Lenka, Palička, Vladimír, Hyršlová Vaculová, Alena
Format:	Journal Article
Language:	English
Published:	Switzerland 01-02-2022
Subjects:	Biotransformation Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Cell Line, Tumor Cytochrome P-450 CYP1A2 - metabolism Down-Regulation Gene Expression Regulation, Neoplastic Hepatocytes - metabolism Humans Liver Neoplasms - genetics Liver Neoplasms - metabolism MicroRNAs - metabolism Xenobiotics - metabolism Hepatocellular carcinoma microRNA AHR Biotransformation CYP1A2
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Summary:	Hepatocellular carcinoma (HCC) is a major contributor to the worldwide cancer burden. Recent studies on HCC have demonstrated dramatic alterations in expression of several cytochrome P450 (CYP) family members that play a crucial role in biotransformation of many drugs and other xenobiotics; however, the mechanisms responsible for their deregulation remain unclear. We investigated a potential involvement of miRNAs in downregulation of expression of CYPs observed in HCC tumors. We compared miRNA expression profiles (TaqMan Array Human MicroRNA v3.0 TLDA qPCR) between HCC human patient tumors with strong (CYP-) and weak/no (CYP+) downregulation of drug-metabolizing CYPs. The role of significantly deregulated miRNAs in modulation of expression of the CYPs and associated xenobiotic receptors was then investigated in human liver HepaRG cells transfected with relevant miRNA mimics or inhibitors. We identified five differentially expressed miRNAs in CYP- versus CYP+ tumors, namely miR-29c, miR-125b1, miR-505, miR-653 and miR-675. The two most-upregulated miRNAs found in CYP- tumor samples, miR-29c and miR-653, were found to act as efficient suppressors of CYP1A2 or AHR expression. Our results revealed a novel role of miR-653 and miR-29c in regulation of expresion of CYPs involved in crucial biotransformation processes in liver, which are often deregulated during liver cancer progression.
ISSN:	1734-1140
DOI:	10.1007/s43440-021-00338-9