ArticleRadiation oncology (London, England)2020
Novel role of PAF1 in attenuating radiosensitivity in cervical cancer by inhibiting IER5 transcription.
Article in Radiation oncology (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Molecular Biomarkers of Radiosensitivity and Radioresistance in Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- PAF1c depletion confers chemoresistance to topoisomerase inhibitors.Cell insight · 2026Article
- IER5 Negatively Regulates Cdc25B Expression in HeLa Cells After Gamma Ray Irradiation.BioMed research international · 2025Article
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- PAF1/HIF1α axis rewires the glycolytic metabolism to fuel aggressiveness of pancreatic cancer.Cancer & metabolism · 2024Article
- Knockdown of PAF1 reduces cervical cancer cell proliferation, migration and invasion via retarding FLOT2-mediated MEK/ERK1/2 pathway.Cell adhesion & migration · 2023Article
- RFX2 promotes tumor cell stemness through epigenetic regulation of PAF1 in spinal ependymoma.Journal of neuro-oncology · 2023Article
- p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment.Cancers · 2023Review
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1.Science advances · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRadiosensitivity is limited in cervical cancer (CC) patients due to acquired radiation resistance. In our previous studies, we found that immediate-early response 5 (IER5) is upregulated in CC cells upon radiation exposure and decreases cell survival by promoting apoptosis. The details on the transcriptional regulation of radiation-induced IER5 expression are unknown. Studies in recent years have suggested that Pol II-associated factor 1 (PAF1) is a pivotal transcription factor for certain genes "induced" during tumor progression. In this study, we investigated the role of PAF1 in regulating IER5 expression during CC radiotherapy.
methodsPAF1 expression in CC cells was measured by western blotting, immunohistochemistry, and qRT-PCR, and the localization of PAF1 and IER5 was determined by immunofluorescence. The effect of PAF1 and IER5 knockdown by siRNA in Siha and Hela cells was studied by western blotting, qRT-PCR, CCK-8 assay, and flow cytometry. The physical interaction of PAF1 with the IER5 promoter and enhancers was confirmed using chromatin immunoprecipitation and qPCR with or without enhancers knockout by CRISPR/Cas9.
resultsWe confirmed that PAF1 was highly expressed in CC cells and that relatively low expression of IER5 was observed in cells with highly expressed PAF1 in the nucleus. PAF1 knockdown in Siha and Hela cells was associated with increased expression of IER5, reduced cell viability and higher apoptosis rate in response to radiation exposure, while simultaneous PAF1 and IER5 knockdown had little effect on the proportion of apoptotic cells. We also found that PAF1 hindered the transcription of IER5 by promoting Pol II pausing at the promoter-proximal region, which was primarily due to the binding of PAF1 at the enhancers.
conclusionsPAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. PAF1 might be a potential therapeutic target for overcoming radiation resistance in CC patients.
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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 Socratic graph.