ArticleJournal of experimental & clinical cancer research : CR2020
MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.Molecular oncology · 2026Article
- MicroRNA320e Augments the Synthetic Lethality of Olaparib by Regulating the PI3K-AKT-mTOR Pathway.Oncology research · 2026Article
- Crosstalk between NRP1 and autophagy in the tumor microenvironment: from molecular mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- Epigenetics in Ovarian Cancer: A Review of Current Knowledge and Future Perspectives.Biomedicines · 2025Review
- miR-490-5p inhibits the progression of osteosarcoma by targeting HDAC2.Translational cancer research · 2025Article
- Exploring the roles and clinical potential of exosome-derived non-coding RNAs in glioma.IBRO neuroscience reports · 2025Review
- Layered Double Hydroxide LDH-Loaded miR-141-3p Targets RAB10 Suppressing Cellular Autophagy to Reverse Paclitaxel Resistance in Breast Cancer.ACS omega · 2025Article
- Article
- Construction of a novel cancer-associated fibroblast-related signature to predict clinical outcome and immune response in cervical cancer.Translational oncology · 2024Article
- Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization ofCells · 2024Article
- The emerging roles of miRNA-mediated autophagy in ovarian cancer.Cell death & disease · 2024Review
- DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection.International journal of molecular sciences · 2024Article
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Discovery of novel PARP1/NRP1 dual-targeting inhibitors with strong antitumor potency.Frontiers in pharmacology · 2024Article
- Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review.Oncology research · 2024Review
- Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2Scientific reports · 2023Article
- Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis.Frontiers of medicine · 2023Article
- MicroRNAs as Potential Biomarkers in Gynecological Cancers.Biomedicines · 2023Review
- Olaparib-ResistantCells · 2023Article
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOvarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance.
methodsUsing three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons' correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells.
resultsWe observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells.
conclusionsThese data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.
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