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

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.

Citation

Galasso, M., Morrison, C., Minotti, L., Corrà, F., Zerbinati, C., Agnoletto, C., …Volinia, S. (2018). Loss of miR-204 expression is a key event in melanoma. Molecular cancer, 17, Article 71. https://doi.org/10.1186/s12943-018-0819-8

• 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