Differentially regulated microRNAs during human sebaceous lipogenesis

Background: MicroRNAs (miRNAs) regulate several aspects of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation has been shown to be associated or even causally related to several skin diseases. Objective: To evaluate the differential expression of miRNAs during sebaceous lipogenesis. Methods: Inhibition of global miRNA activity in human SZ95 sebaceous gland cells was achieved by transfection with siRNAs directed against the DICER transcript, encoding a key enzyme of miRNA biogenesis. Sebaceous lipogenesis was induced in SZ95 sebocytes by addition of linoleic acid (LA) and ciglitazone (CIG) and microarray-based miRNA expression profiles were obtained on an Agilent platform. The expression of selected miRNA candidates was measured by Taqman quantitative real-time RT-PCR. Increased activity of one validated miRNA was attained by transfecting SZ95 sebocytes with miR-574-3p mimics. Results: Downregulation of sebaceous lipogenesis was detected in DICER-impaired SZ95 sebocytes. Using microarrays, we identified twelve significantly upregulated and nine significantly downregulated miRNAs in LA- and CIG-treated SZ95 sebocytes as compared to non-treated cells. Validation of a subset of miRNA candidates by qRT-PCR confirmed upregulation of mIR-203 and miR-574-3p and downregulation of miR-7 during sebaceous lipogenesis. The two upregulated miRNAs have been previously implied in keratinocyte differentiation. Increased activity of miR-574-3p augmented lipogenesis in SZ95 sebocytes. Conclusion: Global miRNA activity is essential for lipid synthesis in human SZ95 sebocytes. Individual miRNAs are likely to play a significant role during sebaceous lipogenesis. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.