Comparative Analysis of Long Noncoding RNA Expression in Human Hepatocyte Cell Lines and Liver
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
Comparative Analysis of Long Noncoding RNA Expression in Human Hepatocyte Cell Lines and Liver O. Y. Bureninaa,*, T. S. Zatsepina,b, E. F. Kimc, A. V. Metelinc, D. A. Skvortsovb,d, M. P. Rubtsovaa,b, and Academician O. A. Dontsovaa,b Received March 10, 2020; revised March 23, 2020; accepted March 23, 2020
Abstract—Long noncoding RNAs (lncRNAs) are promising biomarkers and potential targets for liver cancer therapy. Stable hepatocyte lines are used in vitro to investigate functions of lncRNAs which amount in cell fluctuates during carcinogenesis. For the first time we compared gene expression of known lncRNAs in human conditional normal liver cells HepaRG and cancer cell lines Huh7 and HepG2. We showed that relative amounts of these lncRNAs in HepaRG are close to analogous variables measured for liver samples from healthy donors. Obtained data demonstrate exclusive peculiarities of HepaRG and confirm its reasonable application as a model of normal human hepatocytes for studying functions of lncRNAs. Кeywords: long noncoding RNAs, HepaRG, liver cancer DOI: 10.1134/S1607672920040043
Hepatocellular carcinoma (HCC) is the sixth most common malignant disease in the world. The lack of specific biomarkers along with the asymptomatic course of the disease leads to late diagnosis of this type of cancer and low patient survival rates [1]. Long noncoding RNAs (lncRNAs) are a numerous class of regulatory molecules more than 200 nucleotide residues in length that does not undergo translation. Many lncRNAs are involved in carcinogenesis of hepatocytes and the activity of their gene expression changes significantly during HCC, so that phenomenon can be used both for early diagnostics and potential targeted therapy of this type of cancer [2]. The majority of in vitro HCC studies are conducted using human liver cancer cell lines, most frequently Huh7 and HepG2. Both lines were derived from primary HCC cultures taken from patients (although HepG2 was later annotated as hepatoblastoma [3]), are highly differentiated and possess at least main phenotypic features inherent for tumor liver cells, including the expression of HCC-associated a Center
of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia b Belozersky Institute of Physico-Chemical Biology and Chemistry Department, Moscow State University, Moscow, Russia c Petrovsky National Research Centre of Surgery, Moscow, Russia d Faculty of Biology and Biotechnologies, Higher School of Economics, Moscow, Russia * e-mail: [email protected]
genes [4]. Due to the inability of immortalization of healthy liver cells, primary human hepatocytes are often used as a model culture of liver norm. Unfortunatly, these cultures highly vary from donor to donor, rapidly dedifferentiate and do not have proliferative properties which results into low reproducibility of the experiments. [5]. To date, HepaRG, the product of the company Biopredic (France), is the only cell culture that is phenotypically close to normal human hepatocytes due
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