TY - JOUR
T1 - RMEL3, a novel BRAFV600E-associated long noncoding RNA, is required for MAPK and PI3K signaling in melanoma
AU - Goedert, Lucas
AU - Pereira, Cristiano G.
AU - Roszik, Jason
AU - Plaça, Jessica R.
AU - Cardoso, Cibele
AU - Chen, Guo
AU - Deng, Wanleng
AU - Yennu-Nanda, Vashisht Gopal
AU - Silva, Wilson A.
AU - Davies, Michael A.
AU - Espreafico, Enilza M.
PY - 2016
Y1 - 2016
N2 - Previous work identified RMEL3 as a lncRNA with enriched expression in melanoma. Analysis of The Cancer Genome Atlas (TCGA) data confirmed RMEL3 enriched expression in melanoma and demonstrated its association with the presence of BRAFV600E. RMEL3 siRNA-mediated silencing markedly reduced (95%) colony formation in different BRAFV600E melanoma cell lines. Multiple genes of the MAPK and PI3K pathways found to be correlated with RMEL3 in TCGA samples were experimentally confirmed. RMEL3 knockdown led to downregulation of activators or effectors of these pathways, including FGF2, FGF3, DUSP6, ITGB3 and GNG2. RMEL3 knockdown induces gain of protein levels of tumor suppressor PTEN and the G1/S cyclin-Cdk inhibitors p21 and p27, as well as a decrease of pAKT (T308), BRAF, pRB (S807, S811) and cyclin B1. Consistently, knockdown resulted in an accumulation of cells in G1 phase and subG0/G1 in an asynchronously growing population. Thus, TCGA data and functional experiments demonstrate that RMEL3 is required for MAPK and PI3K signaling, and its knockdown decrease BRAFV600E melanoma cell survival and proliferation.
AB - Previous work identified RMEL3 as a lncRNA with enriched expression in melanoma. Analysis of The Cancer Genome Atlas (TCGA) data confirmed RMEL3 enriched expression in melanoma and demonstrated its association with the presence of BRAFV600E. RMEL3 siRNA-mediated silencing markedly reduced (95%) colony formation in different BRAFV600E melanoma cell lines. Multiple genes of the MAPK and PI3K pathways found to be correlated with RMEL3 in TCGA samples were experimentally confirmed. RMEL3 knockdown led to downregulation of activators or effectors of these pathways, including FGF2, FGF3, DUSP6, ITGB3 and GNG2. RMEL3 knockdown induces gain of protein levels of tumor suppressor PTEN and the G1/S cyclin-Cdk inhibitors p21 and p27, as well as a decrease of pAKT (T308), BRAF, pRB (S807, S811) and cyclin B1. Consistently, knockdown resulted in an accumulation of cells in G1 phase and subG0/G1 in an asynchronously growing population. Thus, TCGA data and functional experiments demonstrate that RMEL3 is required for MAPK and PI3K signaling, and its knockdown decrease BRAFV600E melanoma cell survival and proliferation.
KW - ENSG00000250961
KW - ENST00000506106.1
KW - NcRNA
KW - TCGA
KW - lncRNA
UR - http://www.scopus.com/inward/record.url?scp=84978129474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978129474&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.9164
DO - 10.18632/oncotarget.9164
M3 - Article
C2 - 27167340
AN - SCOPUS:84978129474
SN - 1949-2553
VL - 7
SP - 36711
EP - 36718
JO - Oncotarget
JF - Oncotarget
IS - 24
ER -