Identification of lncRNA-mRNA Regulatory Module to Explore the Pathogenesis and Prognosis of Melanoma

Abstract

Skin cutaneous melanoma (SKCM) is an aggressive form of skin cancer that results in high mortality rate worldwide. It is vital to discover effective prognostic biomarkers and therapeutic targets for the treatment of melanoma. Long non-coding RNA (lncRNA) has been verified to play an essential role in the regulation of gene expression in diseases and tumors. Therefore, it is significant to explore the function of lncRNAs in the development and progression of SKCM. In this paper, a set of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were first screened out using 471 cutaneous melanoma samples and 813 normal skin samples. Gene Ontology and KEGG pathway enrichment analysis were performed to obtain the significant function annotations and pathways of DEmRNAs. We also ran survival analysis on both DElncRNAs and DEmRNAs to identify prognostic-related lncRNAs and mRNAs. Next, a set of hub genes derived from protein-protein interaction (PPI) network analysis and lncRNA target genes screened from starbase-ENCORI database were integrated to construct a lncRNA-mRNA regulatory module, which includes 6 lncRNAs 4 target mRNAs. We further checked the capacity of these lncRNA and mRNA in the diagnosis of melanoma, and found that single lncRNA can effectively distinguish tumor and normal tissue. Moreover, we ran CMap analysis to select a list of small molecule drugs for SKCM, such as EGFR inhibitor AG-490, growth factor receptor inhibitor GW-441756 and apoptosis stimulant betulinic-acid, which have shown therapeutic effect in the treatment of melanoma.