Department of Traditional Chinese and Western Oncology, 36639The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Oncology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221097363. doi: 10.1177/09603271221097363.
This study aimed to clarify the expression and role of hsa_circ_0003159 in gastric carcinogenesis, and validate the protective effects of Icariin (ICA) against gastric cancer (GC) cell growth through the in vitro and in vivo experiments. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and NLRP3 were measured by Quantitative real time Polymerase Chain Reaction or western blot. The cell counting kit (CCK)-8 was used to determine cell proliferation. The target relationship of miR-223-3p/hsa_circ_0003159 and miR-223-3p/NLRP3 was predicted by bioinformatics and validated by the dual-luciferase reporter and pull-down assays. Xenograft model was constructed to assess the roles of hsa_circ_0003159 and protective effects of ICA in GC in vivo. Results showed that hsa_circ_0003159 was downregulated in GC cell lines and its overexpression promoted GC cell viability. MiR-223-3p was identified as a target of hsa_circ_0003159. By competitively sponging miR-223-3p, hsa_circ_0003159 positively regulated NLRP3 expression. MiR-223-3p mimics reversed the suppressive effect of hsa_circ_0003159 on GC cell viability and cell pyroptosis. Importantly, ICA inhibited GC cell viability and triggered GC cell pyroptosis by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 axis in vitro and in vivo. In conclusion, this study indicated ICA inhibits GC cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. This study not only reveals the mechanism of gastric carcinogenesis but also provides potential molecular targets and therapeutic tools for its treatment.
本研究旨在阐明 hsa_circ_0003159 在胃癌发生中的表达和作用，并通过体外和体内实验验证淫羊藿苷（ICA）对胃癌（GC）细胞生长的保护作用。通过定量实时聚合酶链反应或 Western blot 测定 hsa_circ_0003159、微小 RNA（miR）-223-3p 和 NLRP3 的水平。使用细胞计数试剂盒（CCK）-8 测定细胞增殖。通过生物信息学预测 miR-223-3p/hsa_circ_0003159 和 miR-223-3p/NLRP3 的靶关系，并通过双荧光素酶报告和下拉测定验证。构建异种移植模型以评估 hsa_circ_0003159 在体内 GC 中的作用和 ICA 的保护作用。结果表明，hsa_circ_0003159 在 GC 细胞系中下调，其过表达促进 GC 细胞活力。MiR-223-3p 被鉴定为 hsa_circ_0003159 的靶标。通过竞争性海绵吸附 miR-223-3p，hsa_circ_0003159 正向调节 NLRP3 表达。MiR-223-3p 模拟物逆转了 hsa_circ_0003159 对 GC 细胞活力和细胞 pyroptosis 的抑制作用。重要的是，ICA 通过调节 hsa_circ_0003159/miR-223-3p/NLRP3 轴在体外和体内抑制 GC 细胞活力并触发 GC 细胞 pyroptosis。总之，本研究表明 ICA 通过调节 hsa_circ_0003159/miR-223-3p/NLRP3 信号通路抑制 GC 细胞生长。这项研究不仅揭示了胃癌发生的机制，还为其治疗提供了潜在的分子靶点和治疗工具。
