Abstract
The let-7 family is among the first microRNAs found. Recent investigations have indicated that it is highly expressed in many systems, including cerebral and cardiovascular systems. Numerous studies have implicated the aberrant expression of let-7 members in cardiovascular diseases, such as stroke, myocardial infarction (MI), cardiac fibrosis, and atherosclerosis as well as in the inflammation related to these diseases. Furthermore, the let-7 microRNAs are involved in development and differentiation of embryonic stem cells in the cardiovascular system. Numerous genes have been identified as target genes of let-7, as well as a number of the let-7’ regulators. Further studies are necessary to identify the gene targets and signaling pathways of let-7 in cardiovascular diseases and inflammatory processes. The bulk of the let-7’ regulatory proteins are well studied in development, proliferation, differentiation, and cancer, but their roles in inflammation, cardiovascular diseases, and/or stroke are not well understood. Further knowledge on the regulation of let-7 is crucial for therapeutic advances. This review focuses on research progress regarding the roles of let-7 and their regulation in cerebral and cardiovascular diseases and associated inflammation.
Highlights
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YAP translocates into the nucleus and sequesters p72, a DEAD-box helicase 17 (DDX17), which is an essential component of the miRNA processing machinery, Drosha/DGCR8, resulting in downregulation of let-7 (7a and 7b) [99,100]
SNIPP1’ downregulation resulted in let-7i reduction [127], confirming its positive regulation in let-7 biogenesis. Another protein associated with Drosha/DGCR8 complex is synaptotagmin-binding cytoplasmic RNA-interacting protein (SYNCRIP), which was shown to bind to the conserved terminal loop within pri-let-7 [144]
Summary
The let-7 family of microRNAs is one of the earliest originally discovered microRNAs. Let-7a can induce a significant effect on vascular function, as it appears to regulate post-stroke angiogenesis through a transforming growth factor beta 3 (TGF-β3)-dependent mechanism [16]. Post-insult expression of let-7b, which differs from let-7a by a single nucleotide, is associated with greater vascular damage, including in ischemic heart tissue following myocardial infarct (MI) [17]. The elevated presence of let-7b is considered strongly predictive of poor outcome following ischemic stroke [19,20]. Such differences underscore the complexity of let-7’s.
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