Deep sequencing analysis of microRNA expression in human melanocyte and melanoma cell lines

• We used melanocyte cell line (HEMn-LP) and melanoma cell lines (A375 and A2058) to model malignant progression.
• We integrated miRNA and mRNA sequencing data to characterize the melanoma transcriptome.
• Combined network and pathway analysis identified miRNAs regulating melanoma malignancy.
• Analysis of clinical samples and public datasets validated our bioinformatic data on novel and mature miRNAs.

Melanoma is a type of skin cancer that is highly aggressive, and is considered the most deadly of all skin cancers. Currently, there are no effective therapies for melanomas once they undergo metastasis. MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that can post-transcriptionally regulate gene expression. They have been reported to be associated with the occurrence of many diseases, including human melanoma. However, the mechanisms by which miRNAs exert their effects remain unclear; therefore, a systematic analysis of the miRNAome in human melanoma is necessary. We investigated the miRNAome in human melanocyte and melanoma cell lines using high-throughput RNA sequencing. We identified a group of dysregulated miRNAs by comparing the miRNA expression profiles among the melanoma cell lines. Target genes of these miRNAs encode proteins whose functions are associated with the cell cycle and apoptosis. Gene networks were built to investigate the interactions of genes during melanoma progression. We identified that the key genes that regulate melanoma cell proliferation were regulated by miRNAs. In summary, our investigation of the human melanoma miRNAome using high-throughput sequencing revealed a number of previously unreported miRNAs associated with malignant progression of melanoma. Our findings add to existing knowledge regarding the mechanisms of melanoma development.