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

Lookup NU author(s): Professor Nick Reynolds

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Abstract

© 2020 Wiley Periodicals, Inc.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.


Publication metadata

Author(s): Richardson A, Powell AK, Sexton DW, Parsons JL, Reynolds NJ, Ross K

Publication type: Article

Publication status: Published

Journal: Journal of Cellular Physiology

Year: 2020

Volume: 235

Issue: 10

Pages: 6854-6861

Online publication date: 27/01/2020

Acceptance date: 07/01/2020

ISSN (print): 0021-9541

ISSN (electronic): 1097-4652

Publisher: Wiley-Liss Inc.

URL: https://doi.org/10.1002/jcp.29579

DOI: 10.1002/jcp.29579

PubMed id: 31985037


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