ArticleBMC cancer2019
CRKL regulates alternative splicing of cancer-related genes in cervical cancer samples and HeLa cell.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 69 citations in OpenAlex.
- Development of Antagonist Peptides of the Crk/CrkL SH2 Domains by Modifying the Peripheral Amino Acid Residues of the YXXP Motif.Biochemistry · 2026Article
- Integrative analysis of exosomal ncRNAs and their regulatory networks in liver cancer progression.Practical laboratory medicine · 2025Article
- The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL.International journal of molecular sciences · 2025Review
- CPSF4-mediated regulation of alternative splicing of HMG20B facilitates the progression of triple-negative breast cancer.Journal of translational medicine · 2024Article
- Serum proteome profiling of plateau acclimatization in men using Olink proteomics approach.Physiological reports · 2024Article
- scHiClassifier: a deep learning framework for cell type prediction by fusing multiple feature sets from single-cell Hi-C data.Briefings in bioinformatics · 2024Article
- EIF5A2 specifically regulates the transcription of aging-related genes in human neuroblastoma cells.BMC geriatrics · 2023Article
- RALY regulate the proliferation and expression of immune/inflammatory response genes via alternative splicing of FOS.Genes and immunity · 2022Article
- APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer.BMC medical genomics · 2022Article
- Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease.International journal of molecular medicine · 2022Article
- C-C Chemokine Receptor 7 in Cancer.Cells · 2022Review
- Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype.Journal of neurosurgery · 2022Article
- Repression of the expression of proinflammatory genes by mitochondrial transcription factor A is linked to its alternative splicing regulation in human lung epithelial cells.BMC immunology · 2021Article
- Silencing of the CrkL gene reverses the doxorubicin resistance of K562/ADR cells through regulating PI3K/Akt/MRP1 signaling.Journal of clinical laboratory analysis · 2021Article
- Identification of prognostic alternative splicing events in sarcoma.Scientific reports · 2021Article
- Bifunctional Role of CrkL during Bone Remodeling.International journal of molecular sciences · 2021Article
- Review
- Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency.Genes · 2021Review
- Pathways involved in pony body size development.BMC genomics · 2021Article
- Signature of gene aberrant alternative splicing events in pancreatic adenocarcinoma prognosis.Journal of Cancer · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAberrant spliced isoforms are specifically associated with cancer progression and metastasis. The cytoplasmic adaptor CRKL (v-crk avian sarcoma virus CT10 oncogene homolog-like) is a CRK like proto-oncogene, which encodes a SH2 and SH3 (src homology) domain-containing adaptor protein. CRKL is tightly linked to leukemia via its binding partners BCR-ABL and TEL-ABL, upregulated in multiple types of human cancers, and induce cancer cell proliferation and invasion. However, it remains unclear whether signaling adaptors such as CRKL could regulate alternative splicing.
methodsWe analyzed the expression level of CRKL in 305 cervical cancer tissue samples available in TCGA database, and then selected two groups of cancer samples with CRKL differentially expressed to analyzed potential CRKL-regulated alternative splicing events (ASEs). CRKL was knocked down by shRNA to further study CRKL-regulated alternative splicing and the activity of SR protein kinases in HeLa cells using RNA-Seq and Western blot techniques. We validated 43 CRKL-regulated ASEs detected by RNA-seq in HeLa cells, using RT-qPCR analysis of HeLa cell samples and using RNA-seq data of the two group of clinical cervical samples.
resultsThe expression of CRKL was mostly up-regulated in stage I cervical cancer samples. Knock-down of CRKL led to a reduced cell proliferation. CRKL-regulated alternative splicing of a large number of genes were enriched in cancer-related functional pathways, among which DNA repair and G2/M mitotic cell cycle, GnRH signaling were shared among the top 10 enriched GO terms and KEGG pathways by results from clinical samples and HeLa cell model. We showed that CRKL-regulated ASEs revealed by computational analysis using ABLas software in HeLa cell were highly validated by RT-qPCR, and also validated by cervical cancer clinical samples.
conclusionsThis is the first report of CRKL-regulation of the alternative splicing of a number of genes critical in tumorigenesis and cancer progression, which is consistent with CRKL reported role as a signaling adaptor and a kinase. Our results underline that the signaling adaptor CRKL might integrate the external and intrinsic cellular signals and coordinate the dynamic activation of cellular signaling pathways including alternative splicing regulation.
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