ArticleCell death & disease2017
Alternative polyadenylation of ZEB1 promotes its translation during genotoxic stress in pancreatic cancer cells.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Targeting CPSF73, the mRNA 3' end processing endonuclease, moves cancer cells away from the mesenchymal state.Frontiers in immunology · 2026Article
- Alternative splicing impacts microRNA regulation within coding regions.NAR genomics and bioinformatics · 2023Article
- Alternative polyadenylation regulation in cardiac development and cardiovascular disease.Cardiovascular research · 2023Review
- Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications.Journal of experimental & clinical cancer research : CR · 2022Review
- Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.Cancers · 2022Article
- SCAPE: a mixture model revealing single-cell polyadenylation diversity and cellular dynamics during cell differentiation and reprogramming.Nucleic acids research · 2022Article
- The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen.Frontiers in genetics · 2022Review
- Drivers of Gene Expression Dysregulation in Pancreatic Cancer.Trends in cancer · 2021Review
- The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma.Molecular oncology · 2021Article
- Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma.Frontiers in pharmacology · 2021Review
- Observational
- miR-126 targeting GOLPH3 inhibits the epithelial-mesenchymal transition of gastric cancer BGC-823 cells and reduces cell invasion.European journal of histochemistry : EJH · 2020Article
- Circular RNA S-7 promotes ovarian cancer EMT via sponging miR-641 to up-regulate ZEB1 and MDM2.Bioscience reports · 2020Article
- Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma.Genome research · 2020Article
- Alternative Polyadenylation Modification Patterns Reveal Essential Posttranscription Regulatory Mechanisms of Tumorigenesis in Multiple Tumor Types.BioMed research international · 2020Article
- HPV shapes tumor transcriptome by globally modifying the pool of RNA binding protein-binding motif.Aging · 2019Article
- Multifunctional miR-155 Pathway in Avian Oncogenic Virus-Induced Neoplastic Diseases.Non-coding RNA · 2019Review
- miR-1271 inhibits growth, invasion and epithelial-mesenchymal transition by targeting ZEB1 in ovarian cancer cells.OncoTargets and therapy · 2019Article
- MicroRNA-3662 targets ZEB1 and attenuates the invasion of the highly aggressive melanoma cell line A375.Cancer management and research · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy. However, it is not exactly clear how EMT is related to drug resistance or how chemotherapy influences EMT. Herein, we found that ZEB1 is the only EMT-related transcription factor that clearly segregates mesenchymal and epithelial PDAC cell lines. Gemcitabine treatment caused upregulation of ZEB1 protein through post-transcriptional mechanisms in mesenchymal PDAC cells within a context of global inhibition of protein synthesis. The increase in ZEB1 protein correlates with alternative polyadenylation of the transcript, leading to shortening of the 3' untranslated region (UTR) and deletion of binding sites for repressive microRNAs. Polysome profiling indicated that shorter ZEB1 transcripts are specifically retained on the polysomes of PDAC cells during genotoxic stress, while most mRNAs, including longer ZEB1 transcripts, are depleted. Thus, our findings uncover a novel layer of ZEB1 regulation through 3'-end shortening of its transcript and selective association with polysomes under genotoxic stress, strongly suggesting that PDAC cells rely on upregulation of ZEB1 protein expression to withstand hostile environments.
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