Farrer, DJ, Roberts, JC and Ross, K (2016) MicroRNA-9 represses sirtuin 1 (SIRT1) in human keratinocytes. Scholars Bulletin, 2 (9). pp. 525-529. ISSN 2412-897X

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Abstract

The protein deacetylase sirtuin 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 regulate SIRT1 expression in several cell types. Using western blotting, we show that miR-9 represses SIRT1 expression in the HaCaT human keratinocytes. The attenuation of SIRT1 levels 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 of pri-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 expression by miR-9.

Item Type:	Article
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Scholars Middle East Publishers
Date Deposited:	17 Oct 2016 09:48
Last Modified:	04 Sep 2021 12:24
DOI or ID number:	10.21276/sb.2016.2.9.2
URI:	https://researchonline.ljmu.ac.uk/id/eprint/4621

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