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Pigment Cell Melanoma Res. 2019 Mar;32(2):303-314. doi: 10.1111/pcmr.12751. Epub 2018 Dec 16.

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

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Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
Center for Cell-Based Therapy CEPID/FAPESP, Ribeirão Preto, Brazil.
Molecular Oncology Research Center (CPOM) and Melanoma/Sarcoma Surgery Department, Barretos Cancer Hospital, Barretos, Brazil.


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 BRAF-MEK-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.


BRAFV600E; CTD-2023N9.1; ENSG00000250961.1; LncGPBP1-1:1; MAPK; chr5:57395060-57533424 (GRCh38/hg38); melanoma; mitogen; serum response

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