ArticleNucleic acids research2012
Estrogen-induced upregulation and 3'-UTR shortening of CDC6.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 106 citations in OpenAlex.
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- Immunomodulatory role of RNA modifications in sex hormone-dependent cancers.Frontiers in immunology · 2025Review
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- The role of alternative polyadenylation in breast cancer.Frontiers in genetics · 2024Review
- Alternative Transcripts Diversify Genome Function for Phenome Relevance to Health and Diseases.Genes · 2023Review
- CDC6, a key replication licensing factor, is overexpressed and confers poor prognosis in diffuse large B-cell lymphoma.BMC cancer · 2023Article
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- Review
- Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A.eLife · 2023Article
- RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity.BMC cancer · 2023Article
- Glucocorticoids mediate transcriptome-wide alternative polyadenylation: Potential mechanistic and clinical implications.Clinical and translational science · 2022Article
- MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers.Oncogene · 2022Article
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- EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers.Oncogene · 2022Article
- Shortening of the KHDRBS1 3'UTR by alternative cleavage and polyadenylation alters miRNA-mediated regulation and promotes gastric cancer progression.American journal of translational research · 2022Article
- The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen.Frontiers in genetics · 2022Review
- Article
- Identification of an mRNA isoform switch for HNRNPA1 in breast cancers.Scientific reports · 2021Article
- Alternative polyadenylation: An untapped source for prostate cancer biomarkers and therapeutic targets?Asian journal of urology · 2021Review
- A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients.Nature communications · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3'-Untranslated region (UTR) shortening of mRNAs via alternative polyadenylation (APA) has important ramifications for gene expression. By using proximal APA sites and switching to shorter 3'-UTRs, proliferating cells avoid miRNA-mediated repression. Such APA and 3'-UTR shortening events may explain the basis of some of the proto-oncogene activation cases observed in cancer cells. In this study, we investigated whether 17 β-estradiol (E2), a potent proliferation signal, induces APA and 3'-UTR shortening to activate proto-oncogenes in estrogen receptor positive (ER+) breast cancers. Our initial probe based screen of independent expression arrays suggested upregulation and 3'-UTR shortening of an essential regulator of DNA replication, CDC6 (cell division cycle 6), upon E2 treatment. We further confirmed the E2- and ER-dependent upregulation and 3'UTR shortening of CDC6, which lead to increased CDC6 protein levels and higher BrdU incorporation. Consequently, miRNA binding predictions and dual luciferase assays suggested that 3'-UTR shortening of CDC6 was a mechanism to avoid 3'-UTR-dependent negative regulations. Hence, we demonstrated CDC6 APA induction by the proliferative effect of E2 in ER+ cells and provided new insights into the complex regulation of APA. E2-induced APA is likely to be an important but previously overlooked mechanism of E2-responsive gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.