Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression

Ashok Singh, Estelle Willems, Anupama Singh, Bilal Hafeez, Irene M. Ong, Suresh L. Mehta, Ajit Kumar Verma

Research output: Contribution to journalArticle

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Abstract

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).

Original languageEnglish (US)
Pages (from-to)17945-17956
Number of pages12
JournalOncotarget
Volume7
Issue number14
DOIs
StatePublished - Jan 1 2016

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MicroRNAs
Squamous Cell Carcinoma
Tumor Necrosis Factor-alpha
Radiation
Skin
Small Untranslated RNA
RNA Stability
Protein Biosynthesis
Skin Neoplasms
Computational Biology
Phosphatidylinositol 3-Kinases
Knockout Mice
Transforming Growth Factor beta
Real-Time Polymerase Chain Reaction
Cytokines
Radiation Exposure

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression. / Singh, Ashok; Willems, Estelle; Singh, Anupama; Hafeez, Bilal; Ong, Irene M.; Mehta, Suresh L.; Verma, Ajit Kumar.

In: Oncotarget, Vol. 7, No. 14, 01.01.2016, p. 17945-17956.

Research output: Contribution to journalArticle

Singh, Ashok ; Willems, Estelle ; Singh, Anupama ; Hafeez, Bilal ; Ong, Irene M. ; Mehta, Suresh L. ; Verma, Ajit Kumar. / Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression. In: Oncotarget. 2016 ; Vol. 7, No. 14. pp. 17945-17956.
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abstract = "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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