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.

Molecular Carcinogenesis
|December 1, 2022
PubMed

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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