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© 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.
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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