MiR-138-5p Suppresses Cell Growth and Migration in Melanoma by Targeting Telomerase Reverse Transcriptase

Abstract

Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene (<i>hTERT</i>), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of <i>hTERT</i> expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in <i>hTERT</i> regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower <i>hTERT</i> messenger RNA (mRNA) expression in human epidermal melanocytes, compared with melanoma cell lines (A2058, A375, SK-MEL-28) by quantitative polymerase chain reaction (qPCR) observing a negative correlation between them. A2058 melanoma cells were selected to be transfected with miR-138-5p mimic or inhibitor. Using luciferase assay, <i>hTERT</i> was identified as a direct target of this miRNA. Overexpression of miR-138-5p detected by Western blot revealed a decrease in hTERT protein expression (<i>p</i> = 0.012), and qPCR showed a reduction in telomerase activity (<i>p</i> < 0.001). Moreover, suppressions in cell growth (<i>p</i> = 0.035) and migration abilities (<i>p</i> = 0.015) were observed in A2058-transfected cells using thiazolyl blue tetrazolium bromide and flow cytometry, respectively. This study identifies miR-138-5p as a crucial tumor suppressor miRNA involved in telomerase regulation. Targeting it as a combination therapy with immunotherapy or targeted therapies could be used in advanced melanoma treatment; however, more preclinical studies are necessary.