ArticleCancer research2019
A PolH Transcript with a Short 3'UTR Enhances PolH Expression and Mediates Cisplatin Resistance.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Investigation of radiation-induced DNA damage repair-related genes as diagnostic biomarkers for radiation.Journal of radiation research · 2025Article
- Review
- Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.Cancer science · 2024Article
- A New Drug Discovery Platform: Application to DNA Polymerase Eta and Apurinic/Apyrimidinic Endonuclease 1.International journal of molecular sciences · 2023Article
- Alternative polyadenylation reprogramming of MORC2 induced by NUDT21 loss promotes KIRC carcinogenesis.JCI insight · 2023Article
- Article
- Leveraging the replication stress response to optimize cancer therapy.Nature reviews. Cancer · 2023Review
- Context-specific regulation and function of mRNA alternative polyadenylation.Nature reviews. Molecular cell biology · 2022Review
- Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data.Nature communications · 2022Article
- Response of the Urothelial Carcinoma Cell Lines to Cisplatin.International journal of molecular sciences · 2022Article
- Comprehensive analysis of alternative polyadenylation regulators concerning CD276 and immune infiltration in bladder cancer.BMC cancer · 2022Article
- CYCLIN K down-regulation induces androgen receptor gene intronic polyadenylation, variant expression and PARP inhibitor vulnerability in castration-resistant prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Combination of 7-Aging · 2022Article
- The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen.Frontiers in genetics · 2022Review
- Dynamic Variations of 3'UTR Length Reprogram the mRNA Regulatory Landscape.Biomedicines · 2021Review
- Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features.Nature communications · 2021Article
- DNA Damage Tolerance Pathways in Human Cells: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- Early Drug Discovery and Development of Novel Cancer Therapeutics Targeting DNA Polymerase Eta (POLH).Frontiers in oncology · 2021Article
- Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma.Journal of cell communication and signaling · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Platinum-based anticancer drugs are widely used as a first-line drug for cancers, such as non-small cell lung carcinoma (NSCLC) and bladder cancer. However, the efficacy is limited due to intrinsic or acquired resistance to these drugs. DNA polymerase eta (PolH, Polη) belongs to the Y-family of DNA polymerases and mediates DNA translesion synthesis, a major mechanism for DNA damage tolerance. Here, we showed that a high level of PolH is associated with cisplatin resistance in lung and bladder cancer. Consistent with this, loss of PolH markedly attenuates cisplatin resistance in both cisplatin-sensitive and cisplatin-resistant lung cancer cells. Interestingly, we found that due to the presence of multiple polyadenylation sites, alternative polyadenylation (APA) produces three major PolH transcripts with various lengths of 3'untranslated region (3'UTR; 427-/2516-/6245-nt). We showed that the short PolH transcript with 427-nt 3'UTR is responsible for high expression of PolH in various cisplatin-resistant lung and bladder cancer cell lines. Importantly, loss of the short PolH transcript significantly sensitizes cancer cells to cisplatin treatment. Moreover, we found that miR-619 selectively inhibits the ability of the long PolH transcript with 6245-nt 3'UTR to produce PolH protein and, subsequently, PolH-dependent cell growth. Together, our data suggest that PolH expression is controlled by APA and that the short PolH transcript produced by APA can escape miR-619-mediated repression and, subsequently, confers PolH-mediated cisplatin resistance. SIGNIFICANCE: A short PolH transcript produced by alternative polyadenylation escapes repression by miR-619 and confers resistance to cisplatin.
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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.