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Circ-E-Cad encodes a protein that promotes the proliferation and migration of gastric cancer via the
Fanying Li1, Hongxing Tang1, Shaoji Zhao2
1Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Abstract:
Accumulating studies indicate that circular RNAs (circRNAs) play critical roles in cancer progression. Most of them have been reported to act as microRNA sponges or interact with RNA-binding proteins; however, their full range of functions remains largely unclear. Recently, an increasing number of circRNAs have been found to encode proteins. C-E-Cad, a protein encoded by circular E-cadherin (circ-E-Cad), has been shown to have a great influence in the progression of glioblastoma, but its specific role in gastric cancer (GC) is unclear. Here, we found that both circ-E-Cad and C-E-Cad were upregulated in GC cell lines and GC tissues compared with a human gastric epithelial cell line (GES-1) and normal tissues. Knockdown of circ-E-Cad suppressed GC cell line proliferation and metastasis in vitro and in vivo, whereas overexpression of C-E-Cad had the opposite effects. Immunoblotting revealed that C-E-Cad exerted tumor-promoting functions by regulating the PI3K/AKT pathway. A rescue experiment showed that C-E-Cad but not circ-E-Cad was the executor of protumor biological functions. In addition, we demonstrated that the C-E-Cad expression level could have been increased by the TGF-β/Smad pathway. In summary, our results indicated that the TGF-β/Smad pathway could increase the expression of C-E-Cad to regulate GC cell proliferation, migration, and epithelial-mesenchymal transition by affecting PI3K/AKT signaling.
Insights
Circular E-cadherin (circ-E-Cad) and its encoded protein C-E-Cad are upregulated in gastric cancer. C-E-Cad drives tumor progression by activating the PI3K/AKT pathway, while circ-E-Cad
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer, often acting as miRNA sponges or interacting with proteins.
- While some circRNAs encode proteins, their functions, particularly in gastric cancer (GC), are not fully understood.
- The protein C-E-Cad, encoded by circ-E-Cad, is implicated in glioblastoma, but its role in GC requires elucidation.
Purpose of the Study:
- To investigate the role and mechanism of circ-E-Cad and its encoded protein C-E-Cad in gastric cancer progression.
- To determine the signaling pathways regulated by C-E-Cad in GC.
- To explore the upstream regulation of C-E-Cad expression in GC.
Main Methods:
- Quantitative real-time PCR and Western blotting to assess circ-E-Cad and C-E-Cad expression in GC cell lines and tissues.
- In vitro and in vivo experiments involving knockdown of circ-E-Cad and overexpression of C-E-Cad.
- Analysis of the PI3K/AKT and TGF-β/Smad signaling pathways.
- Rescue experiments to confirm the functional role of C-E-Cad.
Main Results:
- Both circ-E-Cad and C-E-Cad were significantly upregulated in GC cell lines and tissues.
- Knockdown of circ-E-Cad inhibited GC cell proliferation and metastasis.
- Overexpression of C-E-Cad promoted GC cell proliferation and metastasis, primarily by regulating the PI3K/AKT pathway.
- C-E-Cad, not circ-E-Cad, was identified as the key executor of tumor-promoting functions.
- The TGF-β/Smad pathway was found to upregulate C-E-Cad expression.
Conclusions:
- C-E-Cad protein, encoded by circ-E-Cad, plays a crucial tumor-promoting role in gastric cancer.
- C-E-Cad regulates GC cell proliferation, migration, and epithelial-mesenchymal transition via the PI3K/AKT pathway.
- The TGF-β/Smad pathway contributes to gastric cancer progression by increasing C-E-Cad expression.
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