ArticleJournal of experimental & clinical cancer research : CR2022
Flap endonuclease 1 and DNA-PKcs synergistically participate in stabilizing replication fork to encounter replication stress in glioma cells.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 12 citations in OpenAlex.
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Multiple patient-derived glioblastoma models reveal synthetic lethality through concurrent PI3K and CDK4/6 inhibition by blocking trans-active cooperation.Neuro-oncology · 2026Article
- Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage.Molecular and cellular biochemistry · 2025Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS.Journal of biomedical research · 2023Article
- Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy.Biomolecules · 2022Review
- Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSelectively utilizing alternative mechanisms to repair damaged DNA in essential factors deficient cancer facilitates tumor genetic evolution and contributes to treatment resistance. Synthetic lethality strategies provide a novel scenario to anticancer therapy with DNA repair protein mutation, such as glioma with DNA-PKcs-deficiency, a core factor crucial for non-homologous end joining (NHEJ) mediated DNA damage repair. Nevertheless, the clinical significance and molecular mechanisms of synthetic lethality function by interfering tumor DNA replication remain largely unexplored.
methodsCancer clinic treatment resistance-related replication core factors were identified through bioinformatics analysis and RNA-sequencing and verified in clinical specimens by immunoblotting and in situ Proximity Ligation Analysis (PLA). Then, in vitro and in vivo experiments, including visible single molecular tracking system were performed to determine functional roles, the molecular mechanisms and clinical significance of synthetic lethality on glioma tumors.
resultsHyperactive DNA replication and regulator Flap endonuclease 1 (FEN1) provides high efficiency DNA double strand breaks (DSB) repair abilities preventing replication forks collapse during DNA replication which facilitate adaptation to selective pressures. DNA-PKcs deficient glioma cells are highly dependent on FEN1/BRCA1/RAD51 to survival and counteract replication stress. FEN1 protects perturbed forks from erroneous over-resection by MRE11 through regulating of BRCA1-RAD51 and WRN helicase, uncovering an essential genetic interaction between FEN1 and DNA-PKcs in mitigating replication-stress induced tumor genomic instability. Therapeutically, genetic depletion or molecular inhibition of FEN1 and DNA-PKcs perturb glioma progression.
conclusionsOur findings highlight an unanticipated synthetic interaction between FEN1/BRCA1/RAD51 and DNA-PKcs when dysfunction leads to incompatible with cell survival under conditions of interrupted replication progression by disrupting addictive alternative tumor evolution and demonstrate the applicability of combined FEN1 and DNA-PKcs targeting in the treatment of glioma.
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.