microRNA-184 is induced by store-operated calcium entry and regulates early keratinocyte differentiation

Richardson, Adam, Powell, Andrew K, Sexton, Darren W, Parsons, Jason L ORCID: 0000-0002-5052-1125, Reynolds, Nick J and Ross, Kehinde (2020) microRNA-184 is induced by store-operated calcium entry and regulates early keratinocyte differentiation. JOURNAL OF CELLULAR PHYSIOLOGY, 235 (10). pp. 6854-6861.

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Abstract

Extracellular calcium (Ca²⁺ ) and store-operated Ca²⁺ entry (SOCE) govern homoeostasis in the mammalian epidermis. Multiple microRNAs (miRNA) also regulate epidermal differentiation, and raised external Ca²⁺ modulates the expression of several such miRNAs in keratinocytes. However, little is known about the regulation of miR-184 in keratinocytes or the roles of miR-184 in keratinocyte differentiation. Here we report that exogenous Ca²⁺ stimulates miR-184 expression in primary epidermal keratinocytes and that this occurs in a SOCE-dependent manner. Levels of miR-184 were raised by about 30-fold after exposure to 1.5 mM Ca²⁺ for 5 days. In contrast, neither phorbol ester nor 1,25-dihydroxyvitamin D₃ had any effect on miR-184 levels. Pharmacologic and genetic inhibitors of SOCE abrogated Ca²⁺ -dependent miR-184 induction by 70% or more. Ectopic miR-184 inhibited keratinocyte proliferation and led to a fourfold increase in the expression of involucrin, a marker of early keratinocyte differentiation. Exogenous miR-184 also triggered a threefold rise in levels of cyclin E and doubled the levels of γH2AX, a marker of DNA double-strand breaks. The p21 cyclin-dependent kinase inhibitor, which supports keratinocyte growth arrest, was also induced by miR-184. Together our findings point to an SOCE:miR-184 pathway that targets a cyclin E/DNA damage regulatory node to facilitate keratinocyte differentiation.

Item Type:	Article
Uncontrolled Keywords:	DNA damage, keratinocytes, microRNA, skin, store-operated calcium entry
Depositing User:	Symplectic Admin
Date Deposited:	03 Feb 2020 08:28
Last Modified:	19 Jan 2023 00:05
DOI:	10.1002/jcp.29579
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3072671