Monday, March 8, 2021

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

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Abstract

Background

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.

Objectives

To understand the molecular basis underlying the lower incidence of NMSC observed in patients with vitiligo by investigating their miRNA‐regulated gene networks.

Methodology

We used data sets from our previously published studies on vitiligo epidermis to construct functional miRNA‐mRNA networks. MiRtarbase was used to fetch the experimentally validated targets of DE‐miRNAs. Protein‐protein interaction (PPI) networks were constructed with only those gene targets that demonstrated a pattern of inverse regulation with their upstream miRNAs. 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.

Results

Two PPI networks were constructed for the miRNA–mRNA interactions (230 down‐regulated targets of 5 up‐regulated miRNAs and 47 up‐regulated mRNAs targeted by 12 down‐regulated miRNAs). Pathway enrichment analysis identified RNA biogenesis and transport as well as cell adhesion to be perturbed in vitiligo. We further 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 overexpressed in SCC or BCC.

Conclusion

We identified a perturbed miRNA‐regulated transcriptome, which potentially confers protection to vitiligo skin from an increased incidence of NMSC.

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