Long Noncoding RNA LL35/Falcor Regulates Expression of Transcription Factor Foxa2 in Hepatocytes in Normal and Fibrotic Mouse Liver

O V Sergeeva; S A Korinfskaya; I I Kurochkin; T S Zatsepin

doi:10.32607/20758251-2019-11-3-66-74

Long Noncoding RNA LL35/Falcor Regulates Expression of Transcription Factor Foxa2 in Hepatocytes in Normal and Fibrotic Mouse Liver

Acta Naturae. 2019 Jul-Sep;11(3):66-74. doi: 10.32607/20758251-2019-11-3-66-74.

Authors

O V Sergeeva¹, S A Korinfskaya¹, I I Kurochkin¹, T S Zatsepin^{1

2}

Affiliations

¹ Skolkovo Institute of Science and Technology, Bolshoy Blvd. 30, bldg. 1, Moscow, 121205, Russia.
² Department of Chemistry, Lomonosov Moscow State University, Leninsikie gory 1, bldg. 3, Moscow, 119991, Russia.

Abstract

Long noncoding RNAs (lncRNA) play important roles in the regulation of transcription, splicing, translation, and other processes in the cell. Human and mouse lncRNA (DEANR1 and LL35/Falcor, respectively) located in the genomic environment in close proximity to the Foxa2 transcription factor were discovered earlier. In this work, tissue-specific expression of LL35/Falcor lncRNA has been shown in mouse liver and lungs. The use of antisense oligonucleotides allowed us to achieve LL35/Falcor lncRNA downregulation by 90%. As a result, the level of Foxa2 mRNA and protein dropped, which confirms the involvement of LL35/Falcor lncRNA in the regulation of transcription factor Foxa2. We have shown a decrease in the expression of LL35 lncRNA in liver fibrosis, which correlates with the previously published data for mRNA Foxa2. Thus, lncRNA LL35 regulates Foxa2 expression in the liver not only in normal conditions, but also during development of fibrosis, which allows one to consider lncRNA a biomarker of this pathological process.

Keywords: liver; non-coding RNA; regulation; transcription factor Foxa2.