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Updated: Mar 29, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
miR-211 and MITF modulation by Bcl-2 protein in melanoma cells
Teresa De Luca1, Andrea Pelosi2, Daniela Trisciuoglio1
1Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
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. © 2015 Wiley Periodicals, Inc.
Insights
Bcl-2 oncogene overexpression in melanoma reduces oncosuppressor miR-211 levels, impacting cell migration and gene expression. This suggests Bcl-2 influences melanoma progression by modulating miR-211 and related pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Melanoma, a deadly skin cancer, involves genetic alterations, including the Bcl-2 oncogene.
- MicroRNAs (miRNAs) are key regulators of melanoma development; miR-211 acts as an oncosuppressor.
Purpose of the Study:
- To investigate the correlation between Bcl-2 oncogene expression and miR-211 levels in human melanoma.
- To understand how Bcl-2 influences melanoma progression through miR-211 modulation.
Main Methods:
- Utilized human melanoma cell lines with stable Bcl-2 overexpression.
- Employed Western blot, quantitative real-time PCR, immunofluorescence, and chromatin immunoprecipitation assays.
Main Results:
- Bcl-2 overexpression led to reduced pri-miR-211, miR-211, TRPM1, and MLANA expression.
- Increased expression of miR-211 target genes and enhanced cell migration were observed.
- Decreased nuclear localization of microphthalmia-associated transcription factor (MITF) and reduced promoter recruitment were noted.
Conclusions:
- Bcl-2 oncogene overexpression negatively impacts oncosuppressor miR-211 expression in melanoma.
- Bcl-2 modulates melanoma cell migration and gene expression potentially via MITF regulation.
- These findings highlight a novel mechanism of melanoma progression involving Bcl-2 and miR-211.
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