ArticleJournal of experimental & clinical cancer research : CR2021
SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Oncogenic Role of SRPK2 in Different Types of Cancer: A Systematic Review.Journal of cellular and molecular medicine · 2026Pooled it
- Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis.Molecular and cellular biochemistry · 2022Pooled it
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- From splicing to disease: the crucial role of serine/arginine protein kinases in cellular regulation.Molecular biology reports · 2026Review
- Network resilience of the human interactome to pan-cancer mutations reveals conserved pathway vulnerabilities.iScience · 2026Article
- Article
- A novel lncRNA-mediated signaling axis governs cancer stemness and splicing reprogramming in hepatocellular carcinoma with therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Article
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Controlled by disorder: Phosphorylation modulates SRSF1 domain availability for spliceosome assembly.Protein science : a publication of the Protein Society · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- A Novel Missense Variant ofHuman mutation · 2025Article
- Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.Journal of translational medicine · 2024Article
- RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2.Science China. Life sciences · 2024Article
- Article
- Mapping alternative splicing events in colorectal cancer.Discover oncology · 2024Article
- The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.Cancers · 2024Review
- SRPK1 Promotes Glioma Proliferation, Migration, and Invasion through Activation of Wnt/β-Catenin and JAK-2/STAT-3 Signaling Pathways.Biomedicines · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network and key genes in granulosa cells of patients with biochemical primary ovarian insufficiency.Journal of assisted reproduction and genetics · 2024Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe Mnk2 kinase, encoded by MKNK2 gene, plays critical roles in MAPK signaling and was involved in oncogenesis. Human MKNK2 pre-mRNA can be alternatively spliced into two splicing isoforms, the MKNK2a and MKNK2b, thus yielding Mnk2a and Mnk2b proteins with different domains. The involvement of Mnk2 alternative splicing in colon cancer has been implicated based on RNA-sequencing data from TCGA database. This study aimed at investigating the upstream modulators and clinical relevance of Mnk2 alternative splicing in colon adenocarcinoma (CAC).
methodsPCR, western blotting and immunohistochemistry (IHC) were performed to assess the expression of Mnk2 and upstream proteins in CAC. The function of Mnk2 and its regulators were demonstrated in different CAC cell lines as well as in xenograft models. Two independent cohorts of CAC patients were used to reveal the clinical significance of MKNK2 alternative splicing.
resultsComparing with adjacent nontumorous tissue, CAC specimen showed a decreased MKNK2a level and an increased MKNK2b level, which were correlated with KRAS mutation and tumor size. The SRSF1 (serine/arginine-rich splicing factor 1) was further confirmed to be the major splicing factor targeting MKNK2 in CAC cells. Higher expression of SRPK1/2 or decreased activity of PP1α were responsible for enhancing SRSF1 phosphorylation and nucleus translocation, subsequently resulted in a switch of MKNK2 alternative splicing.
conclusionsOur data showed that phosphorylation and subcellular localization of SRSF1 were balanced by SRPK1/2 and PP1α in CAC cells. High nucleus SRSF1 promoted MKNK2 splicing into MKNK2b instead of MNK2a, consequently enhanced tumor proliferation.
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