ArticleInternational journal of molecular sciences2021
MTHFR Knockdown Assists Cell Defense against Folate Depletion Induced Chromosome Segregation and Uracil Misincorporation in DNA.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Decoding the complex nexus: the mechanistic interplay of hyperhomocysteinemia in brain aging and neurological disorders.Biogerontology · 2026Review
- SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.Cell death & disease · 2026Article
- Prognostic Significance ofBiology · 2025Article
- Uncovering mechanism of hepatotoxicity diseases caused by tetrahydrocannabinol based on novel network toxicology and experimental verification.Scientific reports · 2025Article
- Carbon fluxes rewiring in engineered E. coli via reverse tricarboxylic acid cycle pathway under chemolithotrophic condition.Journal of biological engineering · 2025Article
- Exploring Hepatocellular Carcinoma Pathogenesis: The Influence of Genetic Polymorphisms.Current pharmaceutical design · 2025Review
- Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.Frontiers in immunology · 2024Article
- MTHFR act as a potential cancer biomarker in immune checkpoints blockades, heterogeneity, tumor microenvironment and immune infiltration.Discover oncology · 2023Article
- Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Ketogenic Diet Consumption Inhibited Mitochondrial One-Carbon Metabolism.International journal of molecular sciences · 2022Article
- Downregulation of Methionine Cycle GenesInternational journal of molecular sciences · 2022Article
- MTHFR rs1801131 GG Genotype Combined with Serum LDH Level Predicts Lung Adenocarcinoma Susceptibility and Poor Prognosis in Guangxi Zhuang Population.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Folate depletion causes chromosomal instability by increasing DNA strand breakage, uracil misincorporation, and defective repair. Folate mediated one-carbon metabolism has been suggested to play a key role in the carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. Methylenetetrahydrofolate reductase (MTHFR) is the enzyme catalyzing the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate that can control folate cofactor distributions and modulate the partitioning of intracellular one-carbon moieties. The association between MTHFR polymorphisms and HCC risk is inconsistent and remains controversial in populational studies. We aimed to establish an in vitro cell model of liver origin to elucidate the interactions between MTHFR function, folate status, and chromosome stability. In the present study, we (1) examined MTHFR expression in HCC patients; (2) established cell models of liver origin with stabilized inhibition of MTHFR using small hairpin RNA delivered by a lentiviral vector, and (3) investigated the impacts of reduced MTHFR and folate status on cell cycle, methyl group homeostasis, nucleotide biosynthesis, and DNA stability, all of which are pathways involved in DNA integrity and repair and are critical in human tumorigenesis. By analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that HCC cancer patients with higher MTHFR had a worse survival rate. The shRNA of
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