ArticleCell & bioscience2023
MiR-181a targets STING to drive PARP inhibitor resistance in BRCA- mutated triple-negative breast cancer and ovarian cancer.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022.Frontiers in oncology · 2024Pooled it
- MicroRNAs in Breast Cancer: Biological Functions and Technologies for Experimental and Therapeutic Applications.Cancers · 2026Review
- The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer.International journal of molecular sciences · 2026Review
- Circulating MicroRNA in Breast Cancer.Cancers · 2026Review
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.Journal of extracellular vesicles · 2026Article
- PARP inhibition generates enhanced CD8Nature immunology · 2026Article
- MicroRNA-based strategies to overcome the immunotherapy barrier in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- STING inhibits viral lytic reactivation and cell growth in primary effusion lymphoma.Frontiers in immunology · 2026Article
- Progress and prospects of metal-based immunotherapy in breast cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Defeating miR-181a-3p may potentiate the effect of paclitaxel on G2/M arrest in breast cancer stem cells.Medical oncology (Northwood, London, England) · 2025Article
- Cell-free and extracellular vesicle microRNAs with clinical utility for solid tumors.Molecular oncology · 2025Review
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- Transcriptomic miRNA and mRNA signatures in primary prostate cancer that are associated with lymph-node invasion.Clinical and translational medicine · 2025Article
- cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values.Frontiers in immunology · 2025Review
- Ginsenoside RG3 Synergizes With STING Agonist to Reverse Cisplatin Resistance in Gastric Cancer.Food science & nutrition · 2025Article
- Small Extracellular Vesicles: Unraveling Their Roles in Ovarian Cancer Progression and Tapping Into Clinical Application Potential.International journal of nanomedicine · 2025Review
- The cGAS-STING signaling pathway: emerging targets and challenges in breast cancer immunotherapy.Frontiers in immunology · 2025Review
- Review
- Interferon-induced factor 16 is essential in metastatic melanoma to maintain STING levels and the immune responses upon IFN-γ response pathway activation.Journal for immunotherapy of cancer · 2024Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPoly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-mutated breast cancer (BC), including triple-negative BC (TNBC) and ovarian cancer (OvCa). A key challenge is to identify the factors associated with PARPi resistance; although, previous studies suggest that platinum-based agents and PARPi share similar resistance mechanisms.
methodsOlaparib-resistant (OlaR) cell lines were analyzed using HTG EdgeSeq miRNA Whole Transcriptomic Analysis (WTA). Functional assays were performed in three BRCA-mutated TNBC cell lines. In-silico analysis were performed using multiple databases including The Cancer Genome Atlas, the Genotype-Tissue Expression, The Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, and Gene Omnibus Expression.
resultsHigh miR-181a levels were identified in OlaR TNBC cell lines (p = 0.001) as well as in tumor tissues from TNBC patients (p = 0.001). We hypothesized that miR-181a downregulates the stimulator of interferon genes (STING) and the downstream proinflammatory cytokines to mediate PARPi resistance. BRCA1 mutated TNBC cell lines with miR-181a-overexpression were more resistant to olaparib and showed downregulation in STING and the downstream genes controlled by STING. Extracellular vesicles derived from PARPi-resistant TNBC cell lines horizontally transferred miR-181a to parental cells which conferred PARPi-resistance and targeted STING. In clinical settings, STING levels were positively correlated with interferon gamma (IFNG) response scores (p = 0.01). In addition, low IFNG response scores were associated with worse response to neoadjuvant treatment including PARPi for high-risk HER2 negative BC patients (p = 0.001). OlaR TNBC cell lines showed resistance to platinum-based drugs. OvCa cell lines resistant to platinum showed resistance to olaparib. Knockout of miR-181a significantly improved olaparib sensitivity in OvCa cell lines (p = 0.001).
conclusionmiR-181a is a key factor controlling the STING pathway and driving PARPi and platinum-based drug resistance in TNBC and OvCa. The miR-181a-STING axis can be used as a potential marker for predicting PARPi responses in TNBC and OvCa tumors.
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