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

• Published in: Genes Vol. 12; no. 12; p. 1931
• Main Authors: Tarazón, Estefanía, de Unamuno Bustos, Blanca, Murria Estal, Rosa, Pérez Simó, Gema, Sahuquillo Torralba, Antonio, Simarro, Javier, Palanca Suela, Sarai, Botella Estrada, Rafael
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.11.2021; MDPI
• Subjects: Antibodies; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Chromosome 5; DNA methylation; Experiments; Flow cytometry; Gene amplification; Gene expression; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Immunotherapy; Medical prognosis; Melanocytes; Melanoma; Melanoma, Experimental - genetics; MicroRNAs; MicroRNAs - physiology; miRNA; Mutation; Plasmids; Polymerase chain reaction; Promoter Regions, Genetic; Proteins; RNA, Neoplasm; RNA-directed DNA polymerase; Skin cancer; Telomerase; Telomerase - genetics; Telomerase reverse transcriptase; Tumor suppressor genes; Tumors; United Kingdom > UK; Belgium; United States > US; Germany; miR-138-5p; melanoma; hTERT
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12121931

Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene ( ), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower 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, 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 ( = 0.012), and qPCR showed a reduction in telomerase activity ( < 0.001). Moreover, suppressions in cell growth ( = 0.035) and migration abilities ( = 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.