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

被引：20

作者：

Cardoso, Cibele ^{[1
,2
]}

Serafim, Rodolfo B. ^{[1
]}

Kawakami, Akinori ^{[2
]}

Pereira, Cristiano Goncalves ^{[1
]}

Roszik, Jason ^{[3
]}

Valente, Valeria ^{[1
,4
,5
]}

Vazquez, Vinicius L. ^{[6
,7
]}

Fisher, David E. ^{[2
]}

Espreafico, Enilza M. ^{[1
]}

机构：

[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

来源：

PIGMENT CELL & MELANOMA RESEARCH | 2019年 / 32卷 / 02期

关键词：

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

D O I：

10.1111/pcmr.12751

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：303 / 314

页数：12

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