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Updated: May 31, 2025

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
EIF4A3-Mediated circ_0008126 Inhibits the Progression and Metastasis of Gastric Cancer by Modulating the
Zeen Wang1, Wenxing Chen1, Ziwei Wang1
1Gastrointestinal Surgical Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Background:
Mounting evidence exhibits circRNAs as critical regulators in the progression of many tumors. The regulatory function and potential mechanism by which circ_0008126 in gastric cancer (GC) is unknown.
Methods:
To validate and analyze the expression levels and clinical values of circ_0008126 in GC patients, the biological phenotypes of circ_0008126 in GC were investigated in vitro and in vivo. The roles and effects of circ_0008126 on miR-502-5p, EIF4A3, and APC in GC cells were explored using rescue experiment, RNA stability assay, RNA pull-down, dual-luciferase reporter, RNA immunoprecipitation (RIP), RNA FISH, immunofluorescence (IF), and TOP/Flash and FOP/Flash assays.
Results:
Circ_0008126 expression levels were prominently down-regulated in GC tissues and cells. Importantly, low expression of circ_0008126 was relevant to the more lymphatic metastasis, advanced TNM stage, and poor survival period in patients with GC. Functionally, circ_0008126 inhibited GC cell proliferative activity, metastatic ability, and epithelial-mesenchymal transition (EMT) in vitro and vivo. Mechanistically, we verified that EIF4A3 can mediate the formation of circ_0008126, and circ_0008126 could competitively bind miR-502-5p and alleviate its role and effect on APC, thus inactivating the β-catenin pathway in GC. Additionally, circ_0008126 was determined to increase the stability of APC mRNA by interacting with cytoplasmic EIF4A3 protein and then enhancing the APC expression.
Conclusions:
These data demonstrate that EIF4A3-mediated circ_0008126 could regulate the APC expression and inactivate the β-catenin pathway partly by binding to miR-502-5p and EIF4A3, thus inhibiting the tumorigenesis and development of GC.
Insights
Circular RNA circ_0008126 is downregulated in gastric cancer (GC) and inhibits tumor progression. EIF4A3-mediated circ_0008126 regulates APC expression and inactivates the beta-catenin pathway, suppressing GC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized as key regulators in tumor progression.
- The specific role and underlying mechanisms of circ_0008126 in gastric cancer (GC) remain largely unexplored.
Purpose of the Study:
- To investigate the expression levels and clinical significance of circ_0008126 in GC.
- To elucidate the biological functions and molecular mechanisms of circ_0008126 in GC progression.
Main Methods:
- In vitro and in vivo experiments were conducted to assess GC phenotypes.
- Mechanisms involving miR-502-5p, EIF4A3, and APC were explored using RNA pull-down, dual-luciferase reporter assays, RIP, and RNA FISH.
Main Results:
- Circ_0008126 expression was significantly downregulated in GC tissues and cells, correlating with advanced stage and poor prognosis.
- Circ_0008126 suppressed GC cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT).
- EIF4A3 mediates circ_0008126 formation; circ_0008126 binds miR-502-5p to regulate APC expression and inactivate the beta-catenin pathway, enhancing APC mRNA stability.
Conclusions:
- EIF4A3-mediated circ_0008126 inhibits gastric cancer tumorigenesis and development.
- Circ_0008126 acts by regulating APC expression and inactivating the beta-catenin pathway via interactions with miR-502-5p and EIF4A3.
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