ArticleCell reports2018
Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.Cell death & disease · 2022Pooled it
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- Article
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Unravelling the molecular basis of PARP inhibitor resistance in prostate cancer with homologous recombination repair deficiency.International review of cell and molecular biology · 2024Review
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Prediction of Chemoresistance-How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- MicroRNA-nanoparticles against cancer: Opportunities and challenges for personalized medicine.Molecular therapy. Nucleic acids · 2023Review
- Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles.Nature communications · 2023Article
- Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.Non-coding RNA · 2023Review
- R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance.International journal of molecular sciences · 2023Review
- Ovarian Cancer-Insights into Platinum Resistance and Overcoming It.Medicina (Kaunas, Lithuania) · 2023Review
- Review
- Clinical application of PARP inhibitors in ovarian cancer: from molecular mechanisms to the current status.Journal of ovarian research · 2023Review
- The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.Journal of hematology & oncology · 2022Review
- Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer.International journal of environmental research and public health · 2022Review
- Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers.NPJ breast cancer · 2022Article
- Revisiting chemoresistance in ovarian cancer: Mechanism, biomarkers, and precision medicine.Genes & diseases · 2022Review
- Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair.International journal of molecular sciences · 2022Review
- Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives.Cancers · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
BRCA1/2-mutated ovarian cancers (OCs) are defective in homologous recombination repair (HRR) of double-strand breaks (DSBs) and thereby sensitive to platinum and PARP inhibitors (PARPis). Multiple PARPis have recently received US Food and Drug Administration (FDA) approval for treatment of OCs, and resistance to PARPis is a major clinical problem. Utilizing primary and recurrent BRCA1/2-mutated carcinomas from OC patients, patient-derived lines, and an in vivo BRCA2-mutated mouse model, we identified a microRNA, miR-493-5p, that induced platinum/PARPi resistance exclusively in BRCA2-mutated carcinomas. However, in contrast to the most prevalent resistance mechanisms in BRCA mutant carcinomas, miR-493-5p did not restore HRR. Expression of miR-493-5p in BRCA2-mutated/depleted cells reduced levels of nucleases and other factors involved in maintaining genomic stability. This resulted in relatively stable replication forks, diminished single-strand annealing of DSBs, and increased R-loop formation. We conclude that impact of miR-493-5p on multiple pathways pertinent to genome stability cumulatively causes PARPi/platinum resistance in BRCA2 mutant carcinomas.
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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.