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

Autores de IIS La Fe

• Estefanía Tarazón Melguizo

  Autor

• Blanca De Unamuno Bustos

  Autor

• Rosa María Murria Estal

  Autor

• Gema Pérez Simó

  Autor

• Antonio Javier Sahuquillo Torralba

  Autor

• Javier Simarro Farinos

  Autor

• Sarai Palanca Suela

  Autor

• 

  Rafael Botella Estrada

  Autor

Grupos

• Dermatología y Regeneración Tisular

• Grupo de Investigación Clínica y Traslacional en Cardiología

• Investigación Clínica y Traslacional en Cáncer

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.

Keywords

• *hTERT; *melanoma; *miR-138-5p