EGCG-LYS Fibrils-Mediated CircMAP2K2 Silencing Decreases the Proliferation and Metastasis Ability of Gastric Cancer Cells in Vitro and in Vivo

作者：Dong, Jiaqi; Zheng, Zhousan; Zhou, Mi; Wang, Yunfei; Chen, Jiajie; Cen, Junjie; Cao, Tiefeng; Yang, Taowei; Xu, Yi; Shu, Guannan; Lu, Xuanxuan^*; Liang, Yanping^*

来源：Advanced Science, 2023.

DOI：10.1002/advs.202304075

• circRNAs
• gastric cancer
• nanocarriers
• small interfering RNA

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer-related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome-mediated degradation, which further mediates the activation of the AKT/GSK3 & beta;/epithelial-to-mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin-3-gallate-lysozyme (EGCG-LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG-LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG-LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post-transcriptional gene silencing. In addition, EGCG-LYS carrying si-circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG-LYS fibrils delivery system provides a new tool and approach for the treatment of GC. @@@ CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome-mediated degradation, resulting in an epithelial-to-mesenchymal transition (EMT)-like phenotype, and activated AKT/GSK3 & beta; signaling pathway enhances proliferation and metastasis of gastric cancer. In addition, EGCG-LYS/si-circMAP2K2 nanocarrier delivery system of small interfering RNA can effectively and safely deliver siRNA system to the tumor and has the function of knocking down target genes, providing a new tool and approach for the treatment of gastric cancer.image

• 单位
  东莞市人民医院; 中山大学; 南方医科大学; 1