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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00075993" target="_blank" >RIV/65269705:_____/22:00075993 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/22:00555407 RIV/00216224:14310/22:00125067 RIV/00179906:_____/22:10449864 RIV/00209805:_____/22:00078890

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s43440-021-00338-9" target="_blank" >https://link.springer.com/article/10.1007/s43440-021-00338-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s43440-021-00338-9" target="_blank" >10.1007/s43440-021-00338-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Background 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. Methods 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. Results 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. Conclusions 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. [GRAPHICS] .

Název v anglickém jazyce

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

Popis výsledku anglicky

Background 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. Methods 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. Results 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. Conclusions 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. [GRAPHICS] .

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30100 - Basic medicine

Projekt

<a href="/cs/project/NV17-28231A" target="_blank" >NV17-28231A: Exprese biotransformačních enzymů u primárních nádorů jater</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pharmacological Reports

ISSN

1734-1140

e-ISSN

2299-5684

Svazek periodika

74

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

148-158

Kód UT WoS článku

000718694600001

EID výsledku v databázi Scopus

2-s2.0-85119055842