ArticleCell death & disease2024
MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Article
- RNA binding motif protein RBM41 promotes colorectal tumorigenesis by impeding the maturation of NDRG1 pre-mRNA.Cell death discovery · 2026Article
- ADCY7 dictates N-cadherin stability to inhibit HCC metastasis.JHEP reports : innovation in hepatology · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Targeting PAK4 promotes Gemcitabine-induced pyroptosis in pancreatic cancer via NLRP1/caspase-3/GSDME axis.Communications biology · 2026Article
- Biological and prognostic relevance of A-to-I RNA editing across consensus molecular subtypes of colon cancer.Scientific reports · 2026Article
- RNA-binding motif proteins as context-dependent regulators of tumor-immune crosstalk, genome stability, and therapeutic vulnerabilities in cancer.Frontiers in immunology · 2026Review
- COMP promotes the progression of colorectal cancer by regulating epithelial mesenchymal transition.BMC cancer · 2025Article
- Identifying genes associated with Sorafenib resistance in hepatocellular carcinoma to develop risk model.Discover oncology · 2025Article
- In vitro reconstitution of a minimal human centrosome scaffold capable of forming and clustering microtubule asters.Journal of cell science · 2025Article
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Authors and funding
10 authors.
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Abstract
Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.
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