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Exp Dermatol. 2021 Sep;30(9):1309-1319. doi: 10.1111/exd.14317. Epub 2021 Mar 22.

Integrated analysis of miRNA-mRNA networks reveals a strong anti-skin cancer signature in vitiligo epidermis.

Experimental dermatology

Archana Singh, Aayush Gupta, Manish Chowdhary, Hemang D Brahmbhatt

Affiliations

  1. CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  3. Dr. D. Y. Patil Medical College, Pune, Maharashtra, India.

PMID: 33682215 DOI: 10.1111/exd.14317

Abstract

Expression of microRNAs (miRNAs) is often dysregulated in several cancers, including non-melanoma skin cancer (NMSC). Individuals with vitiligo possess a deregulated miRnome along with a lower risk of developing NMSCs. We used data sets from our previously published studies on vitiligo epidermis to construct functional miRNA-mRNA networks to understand the molecular basis underlying the lower incidence of NMSC observed in individuals with vitiligo. miRTarBase database was used to fetch the experimentally validated targets of differentially expressed miRNAs and two protein-protein interaction (PPI) networks were constructed for the miRNA-mRNA interactions (230 downregulated targets of 5 upregulated miRNAs and 47 upregulated mRNAs targeted by 12 downregulated miRNAs). Pathway enrichment analysis identified RNA biogenesis and transport as well as cell adhesion to be perturbed in vitiligo. Further, oncogenic transcription factors (OTFs) that were upregulated in publicly available squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) microarray data were compared with that of vitiligo to decode skin cancer-specific molecular signatures. We identified three significantly upregulated miRNAs, miR-31-5p, miR-31-3p and miR-194-3p in lesional epidermis that could negatively regulate seven oncogenic transcription factors, FOXC1, AR, SP1, YY1, GLI2, TP53 and RARA, known to be over-expressed in SCC or BCC. Taken together, our study identified a perturbed miRNA-regulated transcriptome, which potentially confers protection to vitiligo skin from an increased incidence of NMSC.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords: epidermis; miRNA-mRNA networks; microRNAs; non-melanoma skin cancers; vitiligo

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