| Full text | |
| 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: | 18/04017-9 - Genomic and functional characterization of putative melanoma-restricted lncRNAs (RMELs) |
| Grantee: | Enilza Maria Espreafico |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach |
| Grantee: | Maria Vitória Lopes Badra Bentley |
| Support Opportunities: | 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 Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 13/13465-1 - Functional characterization of HJURP (Holliday junction recognizing protein) in glioblastoma multiforme cells |
| Grantee: | Valeria Valente |
| Support Opportunities: | Regular Research Grants |
| 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 Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| 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 Opportunities: | Scholarships in Brazil - Doctorate |