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

Galasso, M; Morrison, C; Minotti, L; Corra, F; Zerbinati, C; Agnoletto, C; Baldassari, F; Fassan, M; Bartolazzi, A; Di Leva, G; Nuovo, G; Vecchione, A; D'Atri, S; Alvino, E; Previati, M; Nickoloff, B; Croce, C; Volinia, S

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 27, 2018
• Online Publication Date: Mar 9, 2018
• Publication Date: Mar 9, 2018
• Deposit Date: Mar 21, 2018
• Publicly Available Date: Mar 21, 2018
• Journal: Molecular Cancer
• Electronic ISSN: 1476-4598
• Publisher: Springer Verlag
• Volume: 17
• Issue: 71
• DOI: https://doi.org/10.1186/s12943-018-0819-8
• Publisher URL: https://doi.org/10.1186/s12943-018-0819-8
• Related Public URLs: https://molecular-cancer.biomedcentral.com/