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- Title
FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway.
- Authors
Hu, Xiaosi; Zhou, Shuai; Li, Haohao; Wu, Zehui; Wang, Ye; Meng, Lei; Chen, Zhangming; Wei, Zhijian; Pang, Qing; Xu, Aman
- Abstract
Background: Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. Methods: The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). Results: Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. Conclusions: Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.
- Subjects
PI3K/AKT pathway; CELLULAR signal transduction; FORKHEAD transcription factors; STOMACH cancer; OXALIPLATIN
- Publication
Cancer Cell International, 2023, Vol 23, Issue 1, p1
- ISSN
1475-2867
- Publication type
Article
- DOI
10.1186/s12935-023-03077-4