Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press10510.17650/2313-805X-2017-4-3-83-91RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИImpact of HNF4α disrupted expression on hepatocellular carcinoma cells sensitivity to oncogenic pathways inhibitorsВлияние нарушенной экспрессии HNF4α на чувствительность клеток гепатоцеллюлярной карциномы к действию ингибиторов проопухолевых сигнальных каскадовMakarovaA. S.МакароваА. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

KrivtsovaO. M.КривцоваО. М.
Russian Federation

Build. 12, 1 Leninskie Gory, Moscow 119234.

119234 Москва, Ленинские горы, 1, стр. 12.

ChesnokovM. S.ЧесноковМ. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

LazarevichN. I.ЛазаревичН. Л.
Russian Federation

Build. 12, 1 Leninskie Gory, Moscow 119234.

119234 Москва, Ленинские горы, 1, стр. 12.

lazarevich.nl@gmail.comResearch Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.НИИ канцерогенеза ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России.Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaНИИ канцерогенеза ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииBiological Faculty, M.V. Lomonosov Moscow State University.Биологический факультет ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова».150920174383911610201716102017Copyright ©; 2017, Makarova A.S., Krivtsova O.M., Chesnokov M.S., Lazarevich N.I.Copyright ©; 2017, Макарова А.С., Кривцова О.М., Чесноков М.С., Лазаревич Н.Л.2017Makarova A.S., Krivtsova O.M., Chesnokov M.S., Lazarevich N.I.Макарова А.С., Кривцова О.М., Чесноков М.С., Лазаревич Н.Л.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/105

Introduction. Hepatocellular carcinoma (HCC) is characterized by aggressive course, high lethality rate and resistance to current systemic treatment. Analysis of molecular aberrations associated with HCC pathogenesis that control biological properties of HCC allows to evaluate potential efficacy of inhibiting certain oncogenic cascades. The present study is focused on investigation of the impact of reduced expression of the key hepatocyte differentiation regulator, HNF4α, often downregulated in HCC, that influences sensitivity of HCC cells to inhibitors  of the major oncogenic pathways mTOR, CDK4/6-pRb and ROCK.

Materials and methods. Changes in cells proliferation and migration caused by HNF4А gene stable knockdown were tested in human HCC cell cultures HepG2 and Huh7 followed by examination of these cellular properties under mTOR (rapamycin), CDK4/6 (PD0332991, palbociclib) and ROCK 1/2 (Y27632) inhibitors treatment. Gene expression levels were estimated by the real-time polymerase chain reaction method (Real-Time PCR).

Results. HNF4А gene knockdown alters HepG2 and Huh7 cell migration associated with E-cadherin and N-cadherin expression changes. The HNF4α repression weakens Y27632-induced blockade of HCC cells migration potential. HNF4А gene knockdown causes resistance  of Huh7 cells and increase of HepG2 cells sensitivity to rapamycin and PD0332991 that block cells migration ability.

Conclusions. Expression level of HNF4α renders influence on migration of HCC cells and contributes to their sensitivity to mTOR, CDK4/6 and ROCK1/2 inhibitors’ impact on cell migration activity.

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