ORIGINAL RESEARCH
Role of ACE2/TMPRSS2 genes regulation by intestinal microRNA isoforms in the COVID-19 pathogenesis
1 National Research University Higher School of Economics, Moscow, Russia
2 Lomonosov Moscow State University, Moscow, Russia
3 P. A. Hertsen Moscow Oncology Research Center, branch of the National Medical Research Radiology Center, Moscow, Russia
4 Far Eastern Federal University, Vladivostok, Russia
5 City Clinical Hospital № 15 named after O. M. Filatov, Moscow, Russia
Correspondence should be addressed: Stepan A. Nersisyan
Vavilova, 7, Moscow, 117312; moc.liamg@naysisren.a.s
Funding: the study was supported by the Ministry of Science and Higher Education of the Russian Federation grant (project RFMEFI61618X0092).
Author contribution: Nersisyan SA, Shkurnikov MYu, Osipyants AI, Vechorko VI — study concept; Nersisyan SA, Shkurnikov MYu — bioinformatics analysis; Nersisyan SA, Shkurnikov MYu, Osipyants AI, Vechorko VI — interpretation of results; Nersisyan SA — manuscript writing.
Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.
Keywords: coronavirus, COVID-19, SARS-CoV-2, ACE2, TMPRSS2, miRNA, isomiR, acute respiratory distress syndrome