ArticleJournal of translational medicine2026
MTHFD2 is required for DNA repair and implicated in LUAD radiotherapy resistance.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA damage-based radiotherapy (RT) is a conventional and effective local treatment for lung adenocarcinoma (LUAD). However, residual or recurrent tumors often occur due to radio-resistance. The underlying mechanisms by which radio-resistance occurs are still not fully understood. Novel predictive markers and potential therapeutic targets for LUAD radio-resistance need to be investigated.
methodsBioinformatic tools were used to evaluate the biological functions of MTHFD2 in LUAD patients. The association of MTHFD2 with radiotherapy efficacy in LUAD patients was confirmed by immunohistochemistry. The baseline radioresponsiveness of different LUAD cells was identified and cells with acquired radio-resistance were generated. MTHFD2 in malignant phenotype and DNA damage after irradiation (IR) in LUAD cells were investigated by Western blotting, colony formation and neutral comet assays, etc. LC-MS and co-immunoprecipitation analyses were used to determine the interaction between MTHFD2 and XRCC6. Mouse models were used to verify these effects in vivo.
resultsIn this study, we showed that methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays an important role in intrinsic and acquired radio-resistance in LUAD. High MTHFD2 expression correlates with poor RT response and reduced radiation-induced DNA damage. Mechanistically, MTHFD2 directly interacts with XRCC6 to facilitate XRCC6/XRCC5 complex formation, promoting non-homologous end joining (NHEJ)-mediated repair of DNA double-strand breaks, as evidenced by LC-MS and co-immunoprecipitation (Co-IP).
conclusionsThis study establishes MTHFD2 as a master regulator of NHEJ-mediated radio-resistance through direct interaction with XRCC6. Our findings propose MTHFD2 expression as both a predictive biomarker for radiotherapy stratification and a therapeutic target for radiosensitization in LUAD.
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.