ArticleCell & bioscience2022
N6-methyladenosine-mediated CELF2 regulates CD44 alternative splicing affecting tumorigenesis via ERAD pathway in pancreatic cancer.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- m6A Modification-Mediated LINC01547 Promotes Pancreatic Cancer Growth and Gemcitabine Resistance Through miR-34a-5p/MYH9 Axis.Biochemical genetics · 2026Article
- From matrix to nucleus: CD44 as a central regulator of inflammaging, autophagy, and tissue homeostasis.Biogerontology · 2026Review
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- ALKBH5/IGF2BP1-mediated mCell biology and toxicology · 2026Article
- Modeling epilepsy by loss-of-function of the CUG-binding protein Elav-like family member 2 in zebrafish with multi-omics analysis.Chinese medical journal · 2026Article
- Inhibition of radiotherapy sensitivity in nasopharyngeal carcinoma via the long non-coding RNATranslational cancer research · 2026Article
- Inhibition of PERK-eIF2α-ATF4 signaling enhances the antiviral effects of resveratrol-loaded nanoparticles against enterovirus 71 in hand, foot, and mouth disease.Archives of virology · 2025Article
- Recent Findings in N6-Methyladenosine Modification and Significance in Pancreatic Cancer.Cancer medicine · 2025Review
- TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation.bioRxiv : the preprint server for biology · 2025Article
- Role of the mInternational journal of molecular medicine · 2025Review
- AEnet: a practical tool to construct the splicing-associated phenotype atlas at a single cell level.GigaScience · 2025Article
- Loss of CELF2 promotes skin tumorigenesis and increases drug resistance.International journal of dermatology · 2025Article
- Gene expression profiling of human umbilical vein endothelial cells overexpressing CELF2 as diagnostic targets in diabetes-induced erectile dysfunction.Frontiers in molecular biosciences · 2025Article
- m1A regulator‑mediated methylation modifications and gene signatures and their prognostic value in multiple myeloma.Experimental and therapeutic medicine · 2025Article
- Single-Cell Sequencing and Transcriptome Analysis Explored Changes in Midnolin-Related Immune Microenvironment and Constructed Combined Prognostic Model for Pancreatic Cancer.Journal of inflammation research · 2025Article
- Role and mechanisms of m6A demethylases in digestive system tumors.American journal of cancer research · 2025Review
- Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy.Acta neuropathologica · 2024Article
- m6A regulator-mediated methylation modifications define the immune infiltration characteristics of the tumor microenvironment in prostate adenocarcinoma.Scientific reports · 2024Article
- Integrated Lactylome Characterization Reveals the Molecular Dynamics of Protein Regulation in Gastrointestinal Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
backgroundAlternative splicing (AS) of genes has been found to affect gene stability, and its abnormal regulation can lead to tumorigenesis. CELF2 is a vital splicing factor to participate in mRNA alternative splicing. Its downregulation has been confirmed to promote the occurrence and development of pancreatic cancer (PC). However, the regulatory role and mechanisms in PC has not been elucidated.
resultsCELF2 was downregulated in PC tissues, which affected tumor TNM stage and tumor size, and low expression of CELF2 indicated a poor prognosis of PC. In vivo and in vitro experiments showed that abnormal expression of CELF2 affected the stemness, apoptosis, and proliferation of PC cells. Furthmore, we also found that CELF2 was targeted by ALKBH5 for m6A modification, leading to CELF2 degradation by YTHDF2. Bioinformatic analysis of AS model based on the TCGA database indicated that CELF2 could target CD44 to form different spliceosomes, thereby affecting the biological behavior of PC cells. The conversion of CD44s to CD44V is the key to tumorigenesis. Transcriptomic analysis was conducted to reveal the mechanism of CELF2-mediated CD44 AS in PC. We found that CELF2-mediated splicing of CD44 led to changes in the level of endoplasmic reticulum stress, further regulating the endoplasmic reticulum-associated degradation (ERAD) signaling pathway, thereby affecting apoptosis and cell stemness. In addition, ERAD signaling pathway inhibitor, EerI, could effectively reverse the effect of CD44 on tumors.
conclusionsThis study indicates that N6-methyladenosine-mediated CELF2 promotes AS of CD44, affecting the ERAD pathway and regulating the biological behavior of PC cells. CELF2 is expected to be a new target for targeted-drug development.
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