EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

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



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



Molecular Cell 52(5): 720-733



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 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333659

Download citation: RISBibTeXText

PMID: 24332178

DOI: 10.1016/j.molcel.2013.11.010



Related references

Arabidopsis PTB1 and PTB2 proteins negatively regulate splicing of a mini-exon splicing reporter and affect alternative splicing of endogenous genes differentially. New Phytologist 203(2): 424-436, 2015

Alternative splicing of VEGFA, APP and NUMB genes in colorectal cancer. World Journal of Gastroenterology 21(21): 6550-6560, 2016

Alternative splicing of the cell fate determinant Numb in hepatocellular carcinoma. Hepatology 62(4): 1122-1131, 2016

Retinoids differentially regulate the proliferation of colon cancer cell lines. Experimental Cell Research 233(2): 321-329, 1997

Runx1 exon 6-related alternative splicing isoforms differentially regulate hematopoiesis in mice. Blood 123(24): 3760-3769, 2014

SRSF1 modulates PTPMT1 alternative splicing to regulate lung cancer cell radioresistance. Ebiomedicine 38: 113-126, 2018

Marine- and plant-derived ω-3 fatty acids differentially regulate prostate cancer cell proliferation. Molecular and Clinical Oncology 1(3): 444-452, 2014

NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2. Plos One 6(6): E21585-E21585, 2011

Alternative splicing isoform of T cell factor 4K suppresses the proliferation and metastasis of non-small cell lung cancer cells. Genetics and Molecular Research 14(4): 14009-14018, 2016

QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation. Molecular and Cellular Biology 31(20): 4244-4255, 2011

miR-483-5p promotes prostate cancer cell proliferation and invasion by targeting RBM5. International Braz J Urol 43(6): 1060-1067, 2017

HnRNP A1/A2 and SF2/ASF regulate alternative splicing of interferon regulatory factor-3 and affect immunomodulatory functions in human non-small cell lung cancer cells. Plos One 8(4): E62729-E62729, 2013

Androgens up-regulate transcription of the Notch inhibitor Numb in C2C12 myoblasts via Wnt/β-catenin signaling to T cell factor elements in the Numb promoter. Journal of Biological Chemistry 288(25): 17990-8, 2013

The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition. Biochemical and Biophysical Research Communications 444(3): 445-450, 2014

The mechanism of NUMB regulate tumor proliferation. Sichuan Da Xue Xue Bao. Yi Xue Ban 45(5): 744-748, 2015