title: RMEL3, a novel BRAFV600E-associated long noncoding RNA, is required for MAPK and PI3K signaling in melanoma.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.|National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell-Based Therapy, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Goedert
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cristiano G
authors.initials: CG
authors.lastname: Pereira
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Roszik
authors.affiliation: National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell-Based Therapy, Ribeirão Preto, São Paulo, Brazil.|Clinical Oncology, Stem Cell and Cell Therapy Program, Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Plaça
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cibele
authors.initials: C
authors.lastname: Cardoso
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Wanleng
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Vashisht Gopal
authors.initials: VG
authors.lastname: Yennu-Nanda
authors.affiliation: National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell-Based Therapy, Ribeirão Preto, São Paulo, Brazil.|Department of Genetics, Ribeirão Preto Medical School, and Center for Integrative System Biology (CISBi-NAP/USP), University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.affiliation: Clinical Oncology, Stem Cell and Cell Therapy Program, Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Enilza M
authors.initials: EM
authors.lastname: Espreafico
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D062085:RNA, Long Noncoding; D019869:Phosphatidylinositol 3-Kinases; D048493:Proto-Oncogene Proteins B-raf
keywords: ENSG00000250961; ENST00000506106.1; TCGA; lncRNA; ncRNA