miR-211 and MITF modulation by Bcl-2 protein in melanoma cells

Teresa De Luca, Andrea Pelosi, Daniela Trisciuoglio, Simona D'Aguanno, Marianna Desideri, Valentina Farini, Marta Di Martile, Barbara Bellei, Maria Grazia Tupone, Antonio Candiloro, Giulia Regazzo, Maria Giulia Rizzo, Donatella Del Bufalo

Research output: Contribution to journalArticlepeer-review

Abstract

Melanoma, the most lethal form of skin cancer, is frequently associated with alterations in several genes, among which the Bcl-2 oncogene plays an important role in progression, chemosensitivity and angiogenesis. Also microRNA (miRNA) are emerging as modulators of melanoma development and progression, and among them, miR-211, located within the melastatin-1/TRPM1 (transient receptor potential cation channel, subfamily M, member 1 protein) gene, is prevalently expressed in the melanocyte lineage and acts as oncosuppressor. Using several human melanoma cell lines and their Bcl-2 stably overexpressing derivatives, we evaluated whether there was a correlation between expression of Bcl-2 and miR-211. Western blot analysis and quantitative real-time polymerase chain reaction demonstrated reduced expression of pri-miR-211, miR-211, TRPM1, and MLANA levels, after Bcl-2 overexpression, associated with increased expression of well-known miR-211 target genes. Overexpression of mature miR-211 in Bcl-2 overexpressing cells rescued Bcl-2 ability to increase cell migration. A decreased nuclear localization of microphthalmia-associated transcription factor (MITF), a co-regulator of both miR-211 and TRPM1, and a reduced MITF recruitment at the TRPM1 and MLANA promoters were also evidenced in Bcl-2 overexpressing cells by immunofluorescence and chromatin immunoprecipitation experiments, respectively. Reduction of Bcl-2 expression by small interference RNA confirmed the ability of Bcl-2 to modulate miR-211 and TRPM1 expression.

Original languageEnglish
Pages (from-to)2304-2312
Number of pages9
JournalMolecular Carcinogenesis
Volume55
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Keywords

  • Bcl-2
  • melanoma
  • microRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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