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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The lncRNA RMEL3 protects immortalized cells from serum withdrawal-induced growth arrest and promotes melanoma cell proliferation and tumor growth

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Author(s):
Cardoso, Cibele [1, 2] ; Serafim, Rodolfo B. [1] ; Kawakami, Akinori [2] ; Pereira, Cristiano Goncalves [1] ; Roszik, Jason [3] ; Valente, Valeria [4, 1, 5] ; Vazquez, Vinicius L. [6, 7] ; Fisher, David E. [2] ; Espreafico, Enilza M. [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cell & Mol Biol, Ribeirao Preto - Brazil
[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02115 - USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 - USA
[4] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara - Brazil
[5] Ctr Cell Based Therapy CEPID FAPESP, Ribeirao Preto - Brazil
[6] Barretos Canc Hosp, Mol Oncol Res Ctr CPOM, Barretos - Brazil
[7] Barretos Canc Hosp, Melanoma Sarcoma Surg Dept, Barretos - Brazil
Total Affiliations: 7
Document type: Journal article
Source: PIGMENT CELL & MELANOMA RESEARCH; v. 32, n. 2, p. 303-314, MAR 2019.
Web of Science Citations: 1
Abstract

RMEL3 is a recently identified lncRNA associated with BRAFV600E mutation and melanoma cell survival. Here, we demonstrate strong and moderate RMEL3 upregulation in BRAF and NRAS mutant melanoma cells, respectively, compared to melanocytes. High expression is also more frequent in cutaneous than in acral/mucosal melanomas, and analysis of an ICGC melanoma dataset showed that mutations in RMEL3 locus are preponderantly C > T substitutions at dipyrimidine sites including CC > TT, typical of UV signature. RMEL3 mutation does not correlate with RMEL3 levels, but does with poor patient survival, in TCGA melanoma dataset. Accordingly, RMEL3 lncRNA levels were significantly reduced in BRAFV600E melanoma cells upon treatment with BRAF or MEK inhibitors, supporting the notion that BRAFMEK- ERK pathway plays a role to activate RMEL3 gene transcription. RMEL3 overexpression, in immortalized fibroblasts and melanoma cells, increased proliferation and survival under serum starvation, clonogenic ability, and xenografted melanoma tumor growth. Although future studies will be needed to elucidate the mechanistic activities of RMEL3, our data demonstrate that its overexpression bypasses the need of mitogen activation to sustain proliferation/survival of non-transformed cells and suggest an oncogenic role for RMEL3. (AU)

FAPESP's process: 10/16097-5 - Functional studies and prognostic value of a new gene associated with melanoma progression and oncogenic BRAF
Grantee:Cristiano Gonçalves Pereira
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/13465-1 - Functional characterization of HJURP (Holliday junction recognizing protein) in glioblastoma multiforme cells
Grantee:Valeria Valente
Support type: Regular Research Grants
FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
Grantee:Maria Vitória Lopes Badra Bentley
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/24056-2 - Functional characterization of melanoma-restricted genes (RMELs) associated with melanoma progression and BRAF V600E mutation
Grantee:Cristiano Gonçalves Pereira
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/18189-5 - Studying a possible functional circuitry involving microRNAs, MITF, MYO5A/DLC2, RAB27A and connections with the invasion and metastasis cascade
Grantee:Enilza Maria Espreafico
Support type: Regular Research Grants
FAPESP's process: 18/04017-9 - Genomic and functional characterization of putative melanoma-restricted lncRNAs (RMELs)
Grantee:Enilza Maria Espreafico
Support type: Regular Research Grants
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC