Marco Galasso
Loss of miR-204 expression is a key event in melanoma
Galasso, Marco; Morrison, Carl; Minotti, Linda; Corrà, Fabio; Zerbinati, Carlotta; Agnoletto, Chiara; Baldassari, Federica; Fassan, Matteo; Bartolazzi, Armando; Vecchione, Andrea; Nuovo, Gerard J.; Di Leva, Gianpiero; D’Atri, Stefania; Alvino, Ester; Previati, Maurizio; Nickoloff, Brian J.; Croce, Carlo M.; Volinia, Stefano
Authors
Carl Morrison
Linda Minotti
Fabio Corrà
Carlotta Zerbinati
Chiara Agnoletto
Federica Baldassari
Matteo Fassan
Armando Bartolazzi
Andrea Vecchione
Gerard J. Nuovo
Gianpiero Di Leva g.dileva@keele.ac.uk
Stefania D’Atri
Ester Alvino
Maurizio Previati
Brian J. Nickoloff
Carlo M. Croce
Stefano Volinia
Abstract
Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P =?0.001, Log Odds?=?1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P =?0.001, Log Odds -?1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS.
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 22, 2018 |
Publication Date | Mar 9, 2018 |
Journal | Molecular Cancer |
Print ISSN | 1476-4598 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 17 |
Article Number | 71 |
DOI | https://doi.org/10.1186/s12943-018-0819-8 |
Keywords | BRAF, Breslow, CDKN2A, Keratinocyte, Melanocyte, Melanoma, NRAS, Non coding rna, Somatic alterations, microRNA, Biomarkers, Tumor, Female, Gene Expression, Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Male, MicroRNAs, Mutation, Prognosis |
Publisher URL | http://doi.org/10.1186/s12943-018-0819-8 |
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