MiRNA-dependent regulation of ERBB signaling pathway genes in patients with NASH

by Maria Bograya | Maria Vulf | Daria Shunkina | Ekaterina Karpeeva | Alexandra Komar | Larisa
Litvinova | Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University,
Kaliningrad, Russia 

NAFLD occupies a leading position among internal diseases, and its prevalence among adult
population of Russia is 37%. The development of NAFLD is associated with obesity, type 2
diabetes, dyslipidemia, and metabolic syndrome. Recently, there is increasing evidence for
the role of miRNA in the development of metabolic disorders.
In our study, we first comprehensively analyzed the miRNA profile in NAFLD. Screening of
miRNAs in the blood serum of the studied patients revealed that miRNAs are differentially
expressed in different stages of NAFLD. MiRWalk algorithms were used to identify genes
potentially dysregulated by differentially expressed miRNAs and to functionally enrich
(GSEA) the obtained gene sets using the KEGG and REACTOME databases. One of the
pathways yielded was the ERBB signaling pathway, which leads to the mobilization of
various metabolic pathways. A total of 58 ERBB pathway genes were predicted to be targets
of miRNAs that are elevated in NASH patients. Of particular interest are ERBB4 and its
ligand NRG4, which are most likely targeted by miRNA-15b, miRNA-222-3p, miRNA-423-5p,
and mir-23a-5p. Investigating the mechanisms of the little-studied miRNA-dependent
regulation of the ERBB signaling in the liver is important for finding new participants in the
pathogenesis of liver diseases and/or their diagnostic markers.
This research was funded by State Assignment Grant No. FZWM-2020-0010 and Grant of
the President of the Russian Federation No. MK-2072.2022.3.

MiRNA_ERBB_BGRS_2022