Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research
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Ashok Singh1, Estelle Willems1, Anupama Singh1, Irene M. Ong2, Ajit K. Verma1
1Department of Human Oncology, Wisconsin Institutes for Medical Research, Paul P. Carbone Comprehensive Cancer Center, School of Medicine and Public Health, Madison, WI, 53705, USA
2Biostatistics and Medical Informatics, Medical Science Center, University of Wisconsin, Madison, WI, 53705, USA
Ashok Singh, email: [email protected]
Keywords: microRNA, SKH1 hairless mice, SCC, UVR
Abbreviations: UVR: ultraviolet radiation, SCC: squamous cell carcinoma; microRNA: miRNA
Received: July 13, 2016 Accepted: October 17, 2016 Published: October 26, 2016
Cutaneous squamous cell carcinoma (cSCC) is the most common type of non-melanoma skin cancer that can metastasize. The major etiological factor associated with cSCC is Ultraviolet radiation (UVR) with a limited understanding of its molecular mechanism. It was hypothesized that there is a direct effect of UVR on modulation of microRNAs (miRNAs), a novel class of short noncoding RNAs which affects translation and stability of mRNAs. To test the hypothesis, the dorsal skin of the SKH1 mice (6-7 week old) was exposed to acute and chronic doses of UVR. In miRNA array profiling, we found differential expression (log fold change>1) of miR-25-5p between untreated and acute UVR treated (4kJ/m2) SKH1 mice skin. However, differential expression (>1 log fold) of miR-144-3p, miR-33-5p, miR-32-5p, miR-1983, miR-136-5p, miR-142-3p, miR-376a-3p, miR-142-5p, miR-3968, and miR-29b-3p was observed between untreated and chronically UVR treated mice skin. Differentially expressed selected miRNAs (miR-32-5p, miR-33-5p, miR-144-3p, and miR-376a-3p) were further validated in real time PCR using miRNA specific primers. Web based data mining, for the prediction of potential miRNA associated gene pathways in miRBase database revealed a link with important pathways (PI3K-Akt, MAPK, Wnt, transcriptional misregulation, and other oncogenic pathway) associated with cSCC. Furthermore, findings of PI3K-Akt pathway genes affected due to chronic UVR were confirmed using cDNA array.
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