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Cancer Cell International
Published in: Cancer Cell International 1/2023

Open Access 01-12-2023 | Gastric Cancer | Research

FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway

Authors: Xiaosi Hu, Shuai Zhou, Haohao Li, Zehui Wu, Ye Wang, Lei Meng, Zhangming Chen, Zhijian Wei, Qing Pang, Aman Xu

Published in: Cancer Cell International | Issue 1/2023

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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.
Appendix
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Metadata
Title
FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway
Authors
Xiaosi Hu
Shuai Zhou
Haohao Li
Zehui Wu
Ye Wang
Lei Meng
Zhangming Chen
Zhijian Wei
Qing Pang
Aman Xu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2023
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-023-03077-4

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