Aberrations in the micro-RNA biogenesis machinery and the emerging roles of micro-RNAs in the pathogenesis of cutaneous malignant melanoma

摘要

Micro-RNAs (miRNAs) are small noncoding RNAs that play roles in the posttranscriptional regulation of gene expression. Since the seminal discovery that aberrant miRNA expression has a causative role in leukemogenesis, the involvement of miRNAs in cancer initiation, propagation, and metastasis has been widely studied. In this review, we provide a comprehensive summary of the literature on miRNAs in melanoma, specifically focusing on aberrations in cellular miRNA biogenesis and processing. These aberrations include genetic and epigenetic changes at the chromosomal level, alterations in the level of the miRNA-processing enzyme DICER, and the existence of competitive endogenous RNAs that serve as decoys for miRNAs and thus modulate their effective intracellular concentrations. We also discuss miRNA profiling in melanoma, review several miRNAs implicated in invasion, metastasis, proliferation, and apoptosis, and briefly summarize the cross talk between miRNAs and microphthalmia-associated transcription factor, the master transcriptional regulator of the melanocyte lineage. Finally, we summarize recent studies of miRNA expression as prognostic and predictive biomarkers, as well as initial experiments on the use of miRNAs and small interfering RNAs as therapeutic agents in melanoma.