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MicroRNA‐101 is a Master Regulator of Epigenetic Machinery

MicroRNAs (miRNAs) are small non‐coding RNA molecules that play important role in cellular functions by silencing hundreds to thousands of protein‐coding genes. Considering the function of their target genes, miRNAs have been implicated as key regulators in various physiological and pathological processes. Besides, epigenetic modulations induce heritable changes on gene expression by altering the conformation of chromatin to regulate biological functions as well. Our previous study revealed that several epigenetic modulators were present in a two‐ layered network of microRNA‐101 for regulating HepG2 cell growth. Although cumulating evidence has recently indicated an intricate interplay between miRNAs and epigenetic machinery, the studies that systematically investigate these mechanisms are still lacking. In this study, we incorporated computational and biochemical approaches to delineate the impact of miR‐101 on epigenetic machinery. In miR‐101 over‐expressing HepG2 cells, a significantly altered gene signature of epigenetic machinery was identified by gene‐set enrichment analysis (GSEA). A similar miR‐101‐induced gene‐signature of epigenetic machinery was also identified in human bladder cancer cell line, suggesting that this altered gene signature was not liver‐specific. Comparing to this signature in the cells manipulated with other miRNAs indicated that miR‐101 regulates epigenetic machinery in a specific manner. Furthermore, differential histone post‐translational modifications (PTMs) caused by miR‐101 putative targeting or non‐ targeting epigenetic modifying enzymes were detected by western blotting. Our findings suggest that miR‐101 is a master regulator of epigenetic machinery.