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Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

ABSTRACT: Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

PROVIDER: PRJNA369800 | ENA |

REPOSITORIES: ENA

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Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells [array]

Project description:Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway. By performing small RNA sequencing on A375 melanoma cells and a vemurafenib- resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features. miR-204 is under the control of STAT3 and its expression is induced in amelanotic melanoma cells, where it acts as an effector of vemurafenib’s anti-motility activity by targeting AP1S2. Conversely, miR-211, a known transcriptional target of MITF, is induced in melanotic melanoma cells, where it targets EDEM1 and consequently impairs the degradation of TYROSINASE (TYR) through the ER-associated degradation (ERAD) pathway. In doing so, miR-211 serves as an effector of vemurafenib’s pro-pigmentation activity. We also show that such an increase in pigmentation in turn represents an adaptive response that needs to be overcome using appropriate inhibitors in order to increase the ef cacy of vemurafenib. In summary, we unveil the distinct and context-dependent activities exerted by miR-204 family members in melanoma cells. Our work challenges the widely accepted “same miRNA family = same function” rule and provides a rationale for a novel treatment strategy for melanotic melanomas that is based on the combination of ERK pathway inhibitors with pigmentation inhibitors.

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Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells [miRNA-Seq]

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miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma

Project description:Purpose: Identification of miRNAs that enable resistance to BRAF inhibitors in melanoma suggests a mechanism-based strategy to limit resistance and improve clinical outcomes. Methods: We generated A375 melanoma cells resistant to Vemurafenib (VMF) with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Results: Increased expression of miR-204-5p and miR-211-5p occurring in VMF-resistant cells was determined to impact VMF response.

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Project description:Genome-wide expression analysis of MCF-10A and MCF-7 where miR-204 and miR-211 are overexpressed. The characteristics of differentially expressed genes in both cell lines derives the cells toward being oncogenic.

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Project description:miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma

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MIR-204 target genes

Project description:The aim of this study is to discover genes regulated by miR-204. Differential gene expression in HEK-293 cells transfected with miR-204-mimic compared to HEK-293 cells transfected with control oligo (HEK-293 control) was analyzed using the Agilent Human Whole Genome 4x44K gene expression array (Agilent Technologies, Santa Clara, CA). HEK-293 cells were transfected with either miR-204 or a control, and gene expression was analyzed using the Agilent Human Whole Genome 4x44K array. A dye-swap was performed.

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Project description: Not available

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MIR-204 target genes

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Project description:Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells [array]

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Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells.

Project description: Not available

| S-EPMC5421939 | biostudies-literature