Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression
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Ashok Singh1, Estelle Willems1, Anupama Singh1, Bilal Bin Hafeez1, Irene M. Ong2, Suresh L. Mehta3 and Ajit Kumar Verma1
1 Department of Human Oncology, Wisconsin Institutes for Medical Research, Paul P. Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
2 Biostatistics and Medical Informatics, Medical Science Center, University of Wisconsin, Madison, WI, USA
3 Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
Ajit Kumar Verma, email:
Keywords: microRNA, TNFα, SCC, UVR
Received: November 04, 2015 Accepted: January 29, 2016 Published: February 22, 2016
Chronic exposure to ultraviolet radiation (UVR) is linked to the development of cutaneous squamous cell carcinoma (SCC), a non-melanoma form of skin cancer that can metastasize. Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, is linked to UVR-induced development of SCC. To find clues about the mechanisms by which TNFα may promote UVR-induced development of SCC, we investigated changes in the expression profiling of microRNAs (miRNA), a novel class of short noncoding RNAs, which affects translation and stability of mRNAs. In this experiment, TNFα knockout (TNFα KO) mice and their wild type (WT) littermates were exposed to acute UVR (2.0 kJ/m2) and the expression profiling of epidermal miRNA was determined 4hr post UVR exposure. TNFα deletion in untreated WT mice resulted in differential expression (log fold change>1) of seventeen miRNA. UVR exposure in WT mice induced differential expression of 22 miRNA. However, UVR exposure in TNFα KO mice altered only two miRNAs. Four miRNA, were differentially expressed between WT+UVR and TNFα KO+UVR groups. Differentially expressed selected miRNAs were further validated using real time PCR. Few of the differentially expressed miRNAs (miR-31-5p, miR-196a-5p, miR-127-3p, miR-206-3p, miR-411-5p, miR-709, and miR-322-5p) were also observed in UVR-induced SCC. Finally, bio-informatics analysis using DIANA, MIRANDA, Target Scan, and miRDB algorithms revealed a link with major UVR-induced pathways (MAPK, PI3K-Akt, transcriptional mis-regulation, Wnt, and TGF-beta).
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