Dataset Information
Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway.
Ontology highlight
ABSTRACT: Background
The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms' tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated.Methods
WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway which was regulated by WTX during GC progression was searched by KEGG pathway analysis. The miRNA which monitored WTX expression was screened by miRNA microarray. After verified the pathway and miRNA both in vitro and in vivo, the relationship of miRNA, WTX and the downstream pathway were analyzed by Western blot, immunohistochemistry, RT-PCR, Co-immunoprecipitation (Co-IP), and luciferase analyses.Results
The results showed that WTX serves as a tumour suppressor gene in GC. The loss of WTX which is associated with the aggressiveness of GC by promoting GC cell proliferation in vitro and high metastasis in vivo. Furthermore, WTX expression was positively correlated with the overall survival of GC patients. Microarray assays, bioinformatics analysis, and verification experiments showed that WTX loss activates the PI3K/AKT/mTOR pathway and promotes GC cell proliferation and invasion. And the aberrant miR-20a-5p upregulation contributes to WTX loss in GC, which stimulates PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway and promoted GC progression.Conclusions
The results of the present study elucidated the mechanism of GC progression, which is at least partially caused by aberrant miR-20a-5p upregulation leading to the inhibition of WTX expression and PI3K/AKT/mTOR signaling pathway activation. These findings provide a comprehensive understanding of the action of the miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.
SUBMITTER: Li J
PROVIDER: S-EPMC7545863 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway.
Journal of experimental & clinical cancer research : CR 20201008 1
<h4>Background</h4>The X-linked gene WTX (also called AMER1) has been reported to function as a tumour suppressor gene in Wilms' tumour. In our previous study, WTX expression was shown to be significantly reduced in gastric cancer (GC), but the function and mechanism associated with WTX loss had yet to be fully elucidated.<h4>Methods</h4>WTX expression and clinical significance were father analyzed in GC and control normal gastric tissues, and validated in public databases. The candidate pathway ...[more]