Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Regulation of NUMB alternative splicing by RBM5, RBM6 and RBM10 controls cancer cell proliferation

ABSTRACT: RBM5, a regulator of alternative splicing of apoptotic genes, and its close homologues, RBM6 and RBM10, are RNA binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation and its modulation recapitulates or antagonizes the effects of RBM5, 6 and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation. RNA from 3 biological replicates of knockdowns of RBM5, 6 and 10 and a control set were used. Changes between the control and knockdowns were measured based on using a splice-junction array (Affymetrix HJAY).

ORGANISM(S): Homo sapiens

SUBMITTER: Endre Sebestyen

PROVIDER: E-GEOD-47431 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation.

Bechara Elias G EG Sebestyén Endre E Bernardis Isabella I Eyras Eduardo E Valcárcel Juan J

Molecular cell 20131201 5

RBM5, a regulator of alternative splicing of apoptotic genes, and its highly homologous RBM6 and RBM10 are RNA-binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which ...[more]

PMID: 24332178

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Dataset Information

Regulation of NUMB alternative splicing by RBM5, RBM6 and RBM10 controls cancer cell proliferation

Publications

RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation.

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