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Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2.

PLoS One. 2020 Jul 29;15(7):e0235987. eCollection 2020
Stepan Nersisyan 1 , Maxim Shkurnikov 2 , Andrey Turchinovich 3 , Evgeny Knyazev 4 , Alexander Tonevitsky 4
Stepan Nersisyan 1 , Maxim Shkurnikov 2 , Andrey Turchinovich 3 , Evgeny Knyazev 4 , Alexander Tonevitsky 4

[No authors listed]

Author information
  • 1 Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, Russia.
  • 2 P.A. Hertsen Moscow Oncology Research Center, Branch of National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
  • 3 SciBerg e.Kfm, Mannheim, Germany.
  • 4 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia.

摘要


Development of novel approaches for regulating the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) is becoming increasingly important within the context of the ongoing COVID-19 pandemic since these enzymes play a crucial role in cell infection. In this work we searched for putative ACE2 and TMPRSS2 expression regulation networks mediated by various miRNA isoforms (isomiR) across different human organs using publicly available paired miRNA/mRNA-sequencing data from The Cancer Genome Atlas (TCGA) project. As a result, we identified several miRNA families targeting ACE2 and TMPRSS2 genes in multiple tissues. In particular, we found that lysine-specific demethylase 5B (JARID1B), encoded by the KDM5B gene, can indirectly affect ACE2 / TMPRSS2 expression by repressing transcription of hsa-let-7e / hsa-mir-125a and hsa-mir-141 / hsa-miR-200 miRNA families which are targeting these genes.