Journal
ONCOTARGET
Volume 7, Issue 14, Pages 17945-17956Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7595
Keywords
microRNA; TNF alpha; SCC; UVR
Categories
Funding
- National Institutes of Health [CA102431]
- University of Wisconsin Carbone Cancer Center, Cancer Center Support Grant [P30 CA014520]
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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 (TNFa), a pro-inflammatory cytokine, is linked to UVR-induced development of SCC. To find clues about the mechanisms by which TNFa 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, TNFa knockout (TNFa KO) mice and their wild type (WT) littermates were exposed to acute UVR (2.0 kJ/m(2)) and the expression profiling of epidermal miRNA was determined 4hr post UVR exposure. TNFa 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 TNFa KO mice altered only two miRNAs. Four miRNA, were differentially expressed between WT+ UVR and TNFa 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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