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HNRNPA2B1 confers immune escape of non-small cell lung cancer through targeting lactate/ferroptosis.

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Cell death & disease 📖 저널 OA 97% 2022: 4/4 OA 2023: 6/6 OA 2024: 23/23 OA 2025: 168/168 OA 2026: 148/159 OA 2022~2026 2025 Vol.17(1) p. 49
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Zhang Y, Chen Y, Zhang J, Du X, Huang C

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Immune escape and ferroptosis resistance contribute to non-small cell lung cancer (NSCLC) carcinogenesis.

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APA Zhang Y, Chen Y, et al. (2025). HNRNPA2B1 confers immune escape of non-small cell lung cancer through targeting lactate/ferroptosis.. Cell death & disease, 17(1), 49. https://doi.org/10.1038/s41419-025-08232-5
MLA Zhang Y, et al.. "HNRNPA2B1 confers immune escape of non-small cell lung cancer through targeting lactate/ferroptosis.." Cell death & disease, vol. 17, no. 1, 2025, pp. 49.
PMID 41271615 ↗

Abstract

Immune escape and ferroptosis resistance contribute to non-small cell lung cancer (NSCLC) carcinogenesis. This study aimed to investigate the role of N-methyladenosine (mA) reader heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) in NSCLC immune escape and ferroptosis resistance. HNRNPA2B1 expression was clinically elevated both in the NSCLC samples and single-cell transcriptome sequencing (scRNA-Seq). In vitro co-culture with activated CD8 T cells, HNRNPA2B1 high-expression hampered the CD8 T cell-mediated killing effect and accelerated the immune escape. Besides, the enforced HNRNPA2B1 high-expression alleviated the ferroptosis. Furthermore, HNRNPA2B1 targeted the LDHA mRNA mA modified site to enhance LDHA mRNA stability and lactate accumulation, thereby assisted NSCLC cells to evade CD8 T antitumor immunity and reduced IFN-γ secretion by CD8 T. Furthermore, IFN-γ could stimulate ferroptosis of NSCLC cells. Taken together, these findings revealed an important role for HNRNPA2B1 on NSCLC immune escape and ferroptosis resistance, which provided novel insight into mA modification in NSCLC.

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