ArticleJournal of experimental & clinical cancer research : CR2020
MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer.
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 17 papers.
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17 citing papers in PubMed, 27 citations in OpenAlex.
- Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model.Scientific reports · 2026Article
- Inhibition of dipeptidyl peptidase 9 improves sorafenib sensitivity by inducing ferroptosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2025Article
- p53 transcriptionally activates DCP1B to suppress tumor progression and enhance tumor sensitivity to PI3K blockade in non-small cell lung cancer.Cell death and differentiation · 2025Article
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- MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer.Cancer innovation · 2024Article
- Ferroptosis: Frenemy of Radiotherapy.International journal of molecular sciences · 2024Review
- MicroRNA‑203a‑3p improves bleomycin and pingyangmycin sensitivity by inactivating the PI3K/AKT pathway in hemangioma.Experimental and therapeutic medicine · 2024Article
- Silencing of keratin 15 impairs viability and mobility while facilitating the doxorubicin chemosensitivity by inactivating the β‑catenin pathway in liver cancer.Oncology letters · 2023Article
- Targeting transient receptor potential canonical 1 reduces non‑small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling.Oncology letters · 2023Article
- MAPK4 predicts poor prognosis and facilitates the proliferation and migration of glioma through the AKT/mTOR pathway.Cancer medicine · 2023Article
- PLK4 inhibitor plus bortezomib exhibits a synergistic effect on treating multiple myeloma via inactivating PI3K/AKT signaling.Irish journal of medical science · 2023Article
- Article
- SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- The silencing of miR-199a-5p protects the articular cartilage through MAPK4 in osteoarthritis.Annals of translational medicine · 2022Article
- Article
- A-Kinase Interacting Protein 1 Knockdown Restores ChemosensitivityFrontiers in oncology · 2022Article
- MAPK4 silencing together with a PARP1 inhibitor as a combination therapy in triple‑negative breast cancer cells.Molecular medicine reports · 2021Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCervical cancer is one of the most common cancers among females worldwide and advanced patients have extremely poor prognosis. However, adverse reactions and accumulating resistance to radiation therapy require further investigation.
methodsThe expression levels of mitogen-activated protein kinase 4 (MAPK4) mRNA were analyzed by real-time PCR and its association with overall survival was analyzed using Kaplan-Mier method. Colony formation, immunofluorescence and western blotting were used to examine the effects of MAPK4 knockout or over-expression on cervical cancer cells after radiation treatment. Drug-sensitivity of cervical cancer cells to PARP1 inhibitors, olaparib or veliparib, was analyzed by CCK-8 cell viability assays, and the 50% inhibitory concentration (IC50) was quantified using GraphPad Prism. The functional effects of MAPK4 knockout on the sensitivity of cervical cancer to radiation treatment and PARP1 inhibitors were further examined using xenograft tumor mouse models in vivo.
resultsCervical cancer patients with high MAPK4 mRNA expression have lower survival rate. After radiation treatment, the colony number of MAPK4 knockout cells was markedly reduced, and the markers for DNA double-chain breakage were significantly up-regulated. In addition, MAPK4 knockout reduced protein kinase B (AKT) phosphorylation, whereas its over-expression resulted in opposite effects. In MAPK4 KO cells with irradiation treatment, inhibition of AKT phosphorylation promoted DNA double-chain breakage. Constitutive activation of AKT (CA-AKT) increased the levels of phosphorylated-AKT (p-AKT), and DNA repair-related proteins, phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). Furthermore, MAPK4 knockout was found to affect the sensitivity of cervical cancer cells to poly ADP-ribose polymerase 1 (PARP1) inhibitors by activating the phosphorylation of AKT. Moreover, in vivo results demonstrated that MAPK4 knockout enhanced the sensitivity of cervical cancer to radiation and PARP1 inhibitors in mouse xenograft models.
conclusionsCollectively, our data suggest that combined application of MAPK4 knockout and PARP1 inhibition can be used as therapeutic strategy in radiation treatment for advanced cervical carcinoma.
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