ArticleMolecular oncology2019
HMGA2 as a functional antagonist of PARP1 inhibitors in tumor cells.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- HMGA2 Attenuates Tendon Stem/Progenitor Cell Senescence Via PI3K/AKT-Mediated Mitophagy Activation and SASP Suppression.Stem cell reviews and reports · 2025Article
- HIF-1α-induced long noncoding RNA LINC02776 promotes drug resistance of ovarian cancer by increasing polyADP-ribosylation.Clinical and translational medicine · 2025Article
- HMGA2 interacts with KAT6A to regulate MMPs chromatin architecture and promote triple-negative breast cancer metastasis.Frontiers in immunology · 2025Article
- PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer.Molecular cancer · 2024Article
- Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome.JCI insight · 2024Article
- Review
- Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling.International journal of molecular sciences · 2023Article
- Expression and Clinical Significance of High-Mobility Group AT-hook 2 (HMGA2) in Osteosarcoma.Orthopaedic surgery · 2022Article
- Comparison of Physicochemical, Mechanical, and (Micro-)Biological Properties of Sintered Scaffolds Based on Natural- and Synthetic Hydroxyapatite Supplemented with Selected Dopants.International journal of molecular sciences · 2022Article
- HMGB3 promotes PARP inhibitor resistance through interacting with PARP1 in ovarian cancer.Cell death & disease · 2022Article
- HMGA2 promotes the migration and invasion of gallbladder cancer cells and HMGA2 knockdown inhibits angiogenesis via targeting VEGFA.Molecular medicine reports · 2022Article
- A KLF4/PiHL/EZH2/HMGA2 regulatory axis and its function in promoting oxaliplatin-resistance of colorectal cancer.Cell death & disease · 2021Article
- Influence of Kv11.1 (hERG1) KPflugers Archiv : European journal of physiology · 2021Article
- Resistance Mechanisms to Taxanes and PARP Inhibitors in Advanced Prostate Cancer.Current opinion in endocrine and metabolic research · 2020Article
- MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC.Journal of hematology & oncology · 2020Article
- Oncofetal HMGA2 attenuates genotoxic damage induced by topoisomerase II target compounds through the regulation of local DNA topology.Molecular oncology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly(ADP-ribose) polymerase 1 inhibitors alone or in combination with DNA damaging agents are promising clinical drugs in the treatment of cancer. However, there is a need to understand the molecular mechanisms of resistance to PARP1 inhibitors. Expression of HMGA2 in cancer is associated with poor prognosis for patients. Here, we investigated the novel relationship between HMGA2 and PARP1 in DNA damage-induced PARP1 activity. We used human triple-negative breast cancer and fibrosarcoma cell lines to demonstrate that HMGA2 colocalizes and interacts with PARP1. High cellular HMGA2 levels correlated with increased DNA damage-induced PARP1 activity, which was dependent on functional DNA-binding AT-hook domains of HMGA2. HMGA2 inhibited PARP1 trapping to DNA and counteracted the cytotoxic effect of PARP inhibitors. Consequently, HMGA2 decreased caspase 3/7 induction and increased cell survival upon treatment with the alkylating methyl methanesulfonate alone or in combination with the PARP inhibitor AZD2281 (olaparib). HMGA2 increased mitochondrial oxygen consumption rate and spare respiratory capacity and increased NAMPT levels, suggesting metabolic support for enhanced PARP1 activity upon DNA damage. Our data showed that expression of HMGA2 in cancer cells reduces sensitivity to PARP inhibitors and suggests that targeting HMGA2 in combination with PARP inhibition may be a promising new therapeutic approach.
Indexed as
Identifiers
What OpenQuestion holds
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.