ArticleCell death & disease2025
Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Zfp36l1 Inhibits DNA Damage by Regulating p21-E2F1-Rad51 Signaling During Myogenic Differentiation.International journal of molecular sciences · 2026Article
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Authors and funding
12 authors.
Funding
Abstract
Chemotherapy resistance poses a significant challenge in the treatment of osteosarcoma. While DNA damage repair mechanisms play a crucial role in this resistance, effective intervention strategies remain limited. This study elucidates an intrinsic DNA damage repair mechanism in osteosarcoma cells treated with methotrexate (MTX) that can be effectively disrupted through the overexpression of ZFP36L1. Our findings indicate that ZFP36L1 expression is downregulated in MTX-resistant osteosarcoma cells. By overexpressing ZFP36L1 in osteosarcoma cell lines, we observed an increase in sensitivity to MTX. Further investigation revealed that the overexpression of ZFP36L1 reduces the efficiency of the DNA damage repair process, particularly by inhibiting the DCLRE1C-mediated non-homologous end joining (NHEJ) pathway. Through analysis of the 3' untranslated region (3'UTR) of DCLRE1C mRNA, we identified 8 potential AU-rich elements (AREs) that bind to ZFP36L1. We demonstrated that ZFP36L1 directly interacts with DCLRE1C mRNA, leading to its degradation. In summary, decreased ZFP36L1 expression serves as an inherent mechanism enabling osteosarcoma to develop resistance to MTX therapy. These results highlight ZFP36L1 as a promising therapeutic target for overcoming MTX chemoresistance in osteosarcoma.
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