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Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer

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Li-40-1275-1285-2025.pdf(9.36 MB)
Date
2025
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Authors
Li, Ruijie ; Lv, Mengguo ; Liu, Juan ; Sun, Qian
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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Biología Celular e Histología
DOI
https://doi.org/10.14670/HH-18-853
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info:eu-repo/semantics/article
Description
Abstract
In this study, we investigated the effects of tumor necrosis factor receptor-associated protein 1 (TRAP1) on aerobic glycolysis in cisplatin-resistant lung cancer cells and explored the underlying mechanism. TRAP1 expression levels were determined in cisplatin-resistant lung cancer tissues and A549/CDDP cells. Subsequently, TRAP1 expression in A549/CDDP cells was silenced via small interfering RNA transfection. Moreover, changes in lactate content, glucose consumption, expression levels of lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2), and sensitivity to cisplatin were analyzed. Specifically, the Wnt/β-catenin signaling pathway was examined using the Wnt/β-catenin activator, BML-284. TRAP1 expression levels were higher in cisplatin-resistant tissues and A549/CDDP cells than in cisplatin-sensitive tissues and A549 cells (p<0.05). Moreover, the lactate content, glucose consumption, LDHA, HK2, PKM2 expression levels, and half-maximal inhibitory concentration of cisplatin were all significantly decreased after TRAP1 silencing (p<0.05). Compared with A549 cells, the Wnt/β-catenin pathway was activated in A549/CDDP cells, which was inhibited via TRAP1 silencing. BML-284 reversed the effects of TRAP1 silencing on the aerobic glycolysis and cisplatin sensitivity of A549/CDDP cells. Our findings suggest that TRAP1 affects the cisplatin resistance of lung cancer, possibly by regulating aerobic glycolysis via the Wnt/β-catenin pathway.
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Tumor necrosis factor receptor-related protein 1 , Aerobic glycolysis , Lung cancer , Cisplatin resistance , Wnt/β-catenin
Citation
Histology and Histopathology Vol. 40, nº08 (2025)
URI
http://hdl.handle.net/10201/157371
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Histology and histopathology Vol.40, nº8 (2025)
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