MicroRNA-9 represses sirtuin 1 (SIRT1) in human keratinocytes
Journal Title: Scholars Bulletin - Year 2016, Vol 2, Issue 9
Abstract
Abstract:The protein deacetylasesirtuin 1 (SIRT1) is an established regulator of diverse physiological processes and one of several promising targets for pharmacologic modulation of ageing and longevity. In normal human keratinocytes, SIRT1 has been shown to inhibit proliferation and promote differentiation. MicroRNAs (miRNAs), small non-coding RNA molecules that negatively regulate gene expression, have been shown to control SIRT1 expression in several cell types. Using western blotting, weshow that miR-9 represses SIRT1 expression in HaCaT human keratinocytes. The attenuation of SIRT1levels in response to ectopic miR-9 occurred in a dose-dependent manner. As miR-9 expression is known to be under epigenetic control, the effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was examined. Levels of mature miR-9 increased 8-fold following TSA treatment of HaCaT keratinocytes. Expression of the primary transcripts from which miR-9 is derived was also raised in HaCaT keratinocytes exposed to TSA, with a 7-fold elevation ofpri-miR-9-1 and 4-fold increase of pri-miR-3.In contrast the DNA methyl transferase inhibitor 5-deoxy-azacytidine (DAC)had little effect on miR-9 or primary miR-9 expression. Together, our findings point to a role for chromatin remodelling in regulating miR-9 levels in human keratinocytes and in turn modulation of SIRT1 expressionby miR-9. Keywords: microRNA; keratinocytes; sirtuin1;trichostatin A.
Authors and Affiliations
J. Farrer, J. C. Roberts, K. Ross
Keywords
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