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

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.

Interleukin 8 mediates bcl‐xL‐induced enhancement of human melanoma cell dissemination and angiogenesis in a zebrafish xenograft model

“…Finally, using public microarray and RNA-seq databases of human melanoma patient specimens, we found that there is a positive correlation between bcl-xL and CXCL8 expression, confirming the evidence obtained in vitro with human melanoma cell lines. 4 Indeed, in melanoma specimens, bcl-xL expression correlated with markers of aggressiveness: MITF, a survival factor in melanocytes and melanoma, 45 frequently amplified in this kind of tumor 46 and recently described as being regulated by bcl-xL homolog bcl-2, 47 and SOX10, which promotes primary melanoma and its metastatization 48 and recently proposed as a promising new serum marker for detection of early stage melanoma. 49 Interestingly, it was confirmed that bcl-xL overexpression is able to enhance MITF and SOX10 expression in human melanoma cells and that this increase is counteracted by CXCL8 secretion inhibition.…”

Effects of microRNA-211 on proliferation and apoptosis of lens epithelial cells by targeting SIRT1 gene in diabetic cataract mice

“…A recent study demonstrated that expression of miR-211 increased after down-regulating the level of Bcl-2 [47]. The Bcl-2 expression up-regulated in tissues after transfection of miR-21 mimics and expression of Bax, apoptosis, caspase-3 activity, and the chemosensitivity decreased, indicating miR-21 could promote Bcl-2 expression by combining with the 3′-UTR of Bcl-2 [48].…”

microRNA-378a-5p iS a novel positive regulator of melanoma progression

“…We previously reported Bcl-2 ability to regulate the expression of miR-211 and miR-204, two miRNA involved in melanoma progression and resistance 2 . To evaluate whether the expression of miR-378a-5p was modulated by Bcl-2, we used either Bcl-2 overexpressing clones previously obtained and characterized 2 , or melanoma cells in which Bcl-2 expression was silenced by siRNA 2 . Increased miR-378a-5p expression was found in M14 and A375 cells overexpressing Bcl-2 ( Fig.…”