TY - JOUR
T1 - Loss of miR-204 expression is a key event in melanoma
AU - Galasso, Marco
AU - Morrison, Carl
AU - Minotti, Linda
AU - Corrà, Fabio
AU - Zerbinati, Carlotta
AU - Agnoletto, Chiara
AU - Baldassari, Federica
AU - Fassan, Matteo
AU - Bartolazzi, Armando
AU - Vecchione, Andrea
AU - Nuovo, Gerard J.
AU - Di Leva, Gianpiero
AU - D'Atri, Stefania
AU - Alvino, Ester
AU - Previati, Maurizio
AU - Nickoloff, Brian J.
AU - Croce, Carlo M.
AU - Volinia, Stefano
PY - 2018/3/9
Y1 - 2018/3/9
N2 - 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.
AB - 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.
KW - BRAF
KW - Breslow
KW - CDKN2A
KW - Keratinocyte
KW - Melanocyte
KW - Melanoma
KW - MicroRNA
KW - Non coding rna
KW - NRAS
KW - Somatic alterations
UR - http://www.scopus.com/inward/record.url?scp=85043479974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043479974&partnerID=8YFLogxK
U2 - 10.1186/s12943-018-0819-8
DO - 10.1186/s12943-018-0819-8
M3 - Letter
C2 - 29523154
AN - SCOPUS:85043479974
VL - 17
JO - Molecular Cancer
JF - Molecular Cancer
SN - 1476-4598
IS - 1
M1 - 71
ER -