TY  - JOUR
A1  - Anelli, Viviana
A1  - Ordas, Anita
A1  - Kneitz, Susanne
A1  - Sagredo, Leonel Munoz
A1  - Gourain, Victor
A1  - Schartl, Manfred
A1  - Meijer, Annemarie H.
A1  - Mione, Marina
T1  - Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression
JF  - Frontiers in Genetics
N2  - Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression.
The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc&acc=GSE37015.
KW  - zebrafish
KW  - cancer models
KW  - microRNA
KW  - Jmjd6
KW  - ras
KW  - melanoma
KW  - miR-146a
KW  - miR-193a
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196963
SN  - 1664-8021
VL  - 9
IS  - 675
ER  -