黑色素瘤
生物
RNA结合蛋白
转录组
免疫沉淀
效应器
癌基因
癌症
癌症研究
基因
信使核糖核酸
核糖核酸
计算生物学
基因表达
遗传学
细胞生物学
细胞周期
作者
Metehan Cifdaloz,Lisa Osterloh,Osvaldo Graña‐Castro,Erica Riveiro‐Falkenbach,Pilar Ximénez‐Embún,Javier Muñoz,Cristina Tejedo,Tonantzin G. Calvo,Panagiotis Karras,David Olmeda,Belén Miñana,Marta Cañamero,Estela Cañón,Eduardo Eyras,Haihong Guo,Ferdinand Kappes,Pablo L. Ortiz‐Romero,José Luis Rodríguez‐Peralto,Diego Megı́as,Juan Valcárcel,Marı́a S. Soengas
标识
DOI:10.1038/s41467-017-02353-y
摘要
Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in melanoma after mining the genomic landscape of the 692 known mRBPs across different cancer types. Genome-wide transcriptomic, proteomic, and RNA-immunoprecipitation studies, together with loss-of-function analyses in cell lines, and histopathological evaluation in clinical biopsies, revealed an intricate repertoire of CELF1-RNA interactors with minimal overlap with other malignancies. This systems approach uncovered the oncogene DEK as an unexpected target and downstream effector of CELF1. Importantly, CELF1 and DEK were found to represent early-induced melanoma genes and adverse indicators of overall patient survival. These results underscore novel roles of CELF1 in melanoma, illustrating tumor type-restricted functions of RBPs in cancer.
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