The roles of nuclear miRNAs in cardiovascular disease

MicroRNAs (miRNAs) represent a group of endogenous, single-stranded, small non-coding RNAs. Classically, mature miRNAs are in the cytoplasm where they mediate gene silencing by complementary pairing between their seed sequences (nucleotides 2-8 at the 5' end) and target mRNA 3' untranslated regions. However, many subsequent studies have documented the nuclear localization of miRNAs and unraveled their distinct biological roles beyond canonical cytoplasmic functions. In this review, we summarize the non-canonical roles of nuclear miRNAs in key cardiovascular pathologies to deepen our understanding of the miRNA regulatory network in cardiovascular disease and to provide a theoretical rationale for developing next-generation precision miRNA-targeted therapeutics.