miRNA-486-5p: signaling targets and role in non-malignant disease

MicroRNAs (miRNAs) are short non-coding RNAs, highly conserved between species, that are powerful regulators of gene expression. Aberrant expression of miRNAs alters biological processes and pathways linked to human disease. miR-486-5p is a muscle-enriched miRNA localized to the cytoplasm and nucleus, and is highly abundant in human plasma and enriched in small extracellular vesicles. Studies of malignant and non-malignant diseases, including kidney diseases, have found correlations with circulating miR-486-5p levels, supporting its role as a potential biomarker. Pre-clinical studies of non-malignant diseases have identified miR-486-5p targets that regulate major signaling pathways involved in cellular proliferation, migration, angiogenesis, and apoptosis. Validated miR-486-5p targets include phosphatase and tensin homolog (PTEN) and FoXO1, whose suppression activates phosphatidyl inositol-3-kinase (PI3K)/Akt signaling. Targeting of Smad1/2/4 and IGF-1 by miR-486-5p inhibits transforming growth factor (TGF)-β and insulin-like growth factor-1 (IGF-1) signaling, respectively. Other miR-486-5p targets include matrix metalloproteinase-19 (MMP-19), Sp5, histone acetyltransferase 1 (HAT1), and nuclear factor of activated T cells-5 (NFAT5). In this review, we examine the biogenesis, regulation, validated gene targets and biological effects of miR-486-5p in non-malignant diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04406-y.