ArticleAnnals of translational medicine2021
Forkhead box O1 targeting replication factor C subunit 2 expression promotes glioma temozolomide resistance and survival.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- A DLBCL Prognostic model superior to the IPI score: Mechanistic study and clinical validation based on RFC2- and RFC4-mediated DNA damage repair.Clinical and experimental medicine · 2026Article
- Multiple roles of replication factor C family in pan‑cancer (Review).Oncology reports · 2025Review
- High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype.Cancer cell international · 2024Article
- RFC2 promotes aerobic glycolysis and progression of colorectal cancer.BMC gastroenterology · 2023Article
- Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics.Cancer cell international · 2023Review
- Variable Intrinsic Expression of Immunoregulatory Biomarkers in Breast Cancer Cell Lines, Mammospheres, and Co-Cultures.International journal of molecular sciences · 2023Article
- Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification ofOpen medicine (Warsaw, Poland) · 2023Article
- RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas.Scientific reports · 2022Article
- Cell-cycle and apoptosis related and proteomics-based signaling pathways of human hepatoma Huh-7 cells treated by three currently used multi-RTK inhibitors.Frontiers in pharmacology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdditional mechanisms of temozolomide (TMZ) resistance in gliomas remain uncertain. The aim of this study was to identify another DNA repair mechanism involving forkhead box O1 (FoxO1) and replicator C2 (RFC2) in gliomas.
methodsWe established glioma cells against TMZ, U87R, by exposure to TMZ. Proliferation rate Cell counting kit-8 (CCK8) was used, and epithelial-mesenchymal transition (EMT)-related markers were detected by western blot. The association between FoxO1 and RFC2 was analyzed by heat maps and scatter plot, and Real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of FoxO1 on the expression of RFC2. The regulation effect of FoxO1 on RFC2 expression was analyzed by luciferase reporter gene assay. Knockdown of FoxO1/RFC2 was achieved via short hairpin RNA (shRNA), the effect of knockdown on the proliferation was determined by CCK8 assay and colony formation assay, and apoptosis was examined by flow cytometry and immunoblotting.
resultsThe TMZ-resistant glioma cell line, U87R, was established. The FoxO1 and RFC2 proteins increased significantly in U87R. The expression of FoxO1 and RFC2 were positively related in glioma tissues. We found that FoxO1 contributes to TMZ resistance and cell survival via regulating the expression of RFC2. Moreover, FoxO1 functions as a transcriptional activator to RFC2 by binding to the promoter of RFC2. Furthermore, knockdown of FoxO1/RFC2 suppressed cell proliferation, TMZ resistance, and induced apoptosis in U87R.
conclusionsThe FoxO1/RFC2 signaling pathway promotes glioma cell proliferation and TMZ resistance, suggesting that the FoxO1/RFC2 pathway may be a potential target for TMZ-resistant glioma therapy.
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