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Inducible modulation of miR-204 levels in a zebrafish melanoma model.

ABSTRACT: Here, we present miniCoopR-I, an inducible upgrade of the constitutive miniCoopR vector. We developed miniCoopR-I-sponge-204 and miniCoopR-I-pre-miR-204 vectors and we successfully tested them for their ability to achieve time- (embryo/juvenile/adult) and space- (melanocytic lineage) restricted inhibition/overexpression of miR-204, a positive modulator of pigmentation previously discovered by us. Furthermore, melanoma-free survival curves performed on induced fish at the adult stage indicate that miR-204 overexpression accelerates the development of BRAFV600E-driven melanoma. miniCoopR-I allows study of the impact that coding and non-coding modulators of pigmentation exert on melanomagenesis in adult zebrafish, uncoupling it from the impact that they exert on melanogenesis during embryonic development.This article has an associated First Person interview with the first author of the paper.

SUBMITTER: Sarti S

PROVIDER: S-EPMC7657466 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Inducible modulation of miR-204 levels in a zebrafish melanoma model.

Sarti Samanta S De Paolo Raffaella R Ippolito Chiara C Pucci Angela A Pitto Letizia L Poliseno Laura L

Biology open 20201106 11

Here, we present miniCoopR-I, an inducible upgrade of the constitutive miniCoopR vector. We developed miniCoopR-I-sponge-204 and miniCoopR-I-pre-miR-204 vectors and we successfully tested them for their ability to achieve time- (embryo/juvenile/adult) and space- (melanocytic lineage) restricted inhibition/overexpression of <i>miR-204</i>, a positive modulator of pigmentation previously discovered by us. Furthermore, melanoma-free survival curves performed on induced fish at the adult stage indic ...[more]

PMID: 33037013

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miR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma.

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Loss of miR-204 expression is a key event in melanoma.

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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.

2018-01-18 | GSE107576 | GEO

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.

2012-03-30 | E-GEOD-28400 | biostudies-arrayexpress

miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer's Disease.

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A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.

Project description:The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.

| S-EPMC4868069 | biostudies-literature

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