Role and possible mechanism of pseudogene FMO6P in inhibiting invasion and metastasis of gastric cancer
10.16139/j.1007-9610.2024.02.12
- VernacularTitle:假基因FMO6P抑制胃癌侵袭转移作用及其机制探索
- Author:
Xiongyan WU
1
;
Zhen LI
;
Zhenjia YU
;
Liping SU
Author Information
1. 上海交通大学医学院附属瑞金医院普外科 上海消化外科研究所 上海市胃肿瘤重点实验室,上海 200025
- Keywords:
Gastric cancer;
Pseudogene;
FMO6P;
Tumor metastasis
- From:
Journal of Surgery Concepts & Practice
2024;29(2):161-169
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the expression and clinical significance of pseudogene FMO6P in gastric cancer,and explore its functions and underlying molecular mechanism in regulating the invasion and metastasis of gastric cancer cells.Methods The expression level of FMO6P in gastric cancer tissues and cell lines was detected by quantitative real time polymerase chain reaction(qRT-PCR).The migration and invasion abilities of gastric cancer cells were detected by transwell assay.The effect of FMO6P on the tumor formation and peritoneal dissemination of gastric cancer cells were evaluated by injecting FMO6P-overexpressing gastric cancer cells into the subcutaneous or peritoneal cavity of nude mice respectively.The expression levels of epithelial-mesenchymal transition(EMT)markers,including E-cadherin,N-cadherin,ZEB1,MMP2,and the activation of AKT/mTOR pathway in FMO6P-overexpressing or knockdown gastric cancer cells were measured by Western blot.Results The expression of FMO6P was significantly reduced in tumor tissues compared to its adjacent non-tumor tissues of gastric cancer,FMO6P expression level in tumor tissues was correlated with tumor size and TNM stage.Overexpression of FMO6P significantly inhibited the invasion and migration abilities of gastric cancer cells,while downregulation of FMO6P expression promoted the invasion and migration ability of gastric cancer cells.Overexpression of FMO6P in gastric cancer cells significantly inhibited the subcutaneous tumor formation and peritoneal dissemination of gastric cancer cells in nude mice.Moreover,overexpression of FMO6P promoted the expression of E-cadherin,and inhibited the expression of N-cadherin,ZEB1,and MMP2 in gastric cancer cells.The phosphorylation levels of AKT and mTOR were also downregulated in gastric cancer cells overexpressing FMO6P.Conclusions All these findings suggested that pseudogene FMO6P suppresses the invasion and migration potential of gastric cancer cells in vitro and in vivo,which is possibly through the inhibition of the AKT/mTOR signaling pathway.
