Abstract
Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene (hTERT), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of hTERT expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in hTERT regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower hTERT 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, hTERT 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 (p = 0.012), and qPCR showed a reduction in telomerase activity (p < 0.001). Moreover, suppressions in cell growth (p = 0.035) and migration abilities (p = 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.
Highlights
Melanoma is considered the most dangerous form of skin cancer
Little is known about the role of miRNAs in melanoma human telomerase reverse transcriptase gene (hTERT) regulation
This study identified miR-138-5p as a crucial tumor suppressor miRNA involved in telomerase regulation
Summary
Melanoma is considered the most dangerous form of skin cancer. It represents less than 5% of all cutaneous neoplasms, it is responsible for almost 60% of deaths from skin tumors [1], and its incidence has rapidly increased over the past three decades [2]. The human telomerase reverse transcriptase gene (hTERT) has been implicated in melanoma pathogenesis [4,5]. This gene encodes the catalytic subunit of telomerase that is essential for telomere maintenance and cell senescence regulation. Previous results of our group, as well as those of others, have not identified differences at a protein level between pTERTm carriers and noncarrier tumors [9,12,13,14,15]
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