Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
FASEB J. 2022 Nov;36(11):e22604. doi: 10.1096/fj.202200957RR.
Circular RNAs participate in the pathogenesis of various tumors, including gastric cancer (GC). In this study, we investigated the role of circBGN in regulating proliferation and invasion of GC cells and elucidated the mechanism. The expression of circBGN was assessed by quantitative reverse-transcription PCR and in situ hybridization. In addition, loss- and gain-of-function investigations in vitro and in vivo were performed to determine the biological functions of circBGN. Luciferase reporter assays and rescue experiments were applied to investigate the interaction between circBGN and miR-149-5p as well as the relationship between miR-149-5p and IL6. Our results showed that circBGN expression was significantly elevated in GC tissues and cells. Knockdown of circBGN dramatically suppressed GC cell proliferation and invasion in vitro. Xenograft experiments revealed that knockdown of circBGN delayed tumor growth in vivo. Furthermore, circBGN can directly bind to miR-149-5p, thereby preventing miR-149-5p from binding to its target mRNA [IL6 mRNA], thus activating IL6/STAT3 signaling pathway. Rescue assays indicated that circBGN regulates GC cell proliferation and invasion by upregulating miR-149-5p/IL6 axis output. Taken together, our investigation indicates that circBGN supports GC progression by activating IL6/STAT3 signaling pathway, thus pointing to a new possible therapeutic target in GC.
环状 RNA 参与多种肿瘤的发病机制,包括胃癌(GC)。在本研究中,我们研究了 circBGN 在调节 GC 细胞增殖和侵袭中的作用,并阐明了其机制。通过定量逆转录 PCR 和原位杂交评估 circBGN 的表达。此外,还进行了体外和体内的缺失和功能获得研究,以确定 circBGN 的生物学功能。应用荧光素酶报告基因检测和挽救实验来研究 circBGN 与 miR-149-5p 之间的相互作用以及 miR-149-5p 与 IL6 之间的关系。我们的结果表明,circBGN 在 GC 组织和细胞中表达明显上调。circBGN 的敲低显著抑制了体外 GC 细胞的增殖和侵袭。异种移植实验表明,circBGN 的敲低可延缓体内肿瘤的生长。此外,circBGN 可直接与 miR-149-5p 结合,从而阻止 miR-149-5p 与其靶 mRNA [IL6 mRNA]结合,从而激活 IL6/STAT3 信号通路。挽救实验表明,circBGN 通过上调 miR-149-5p/IL6 轴的输出来调节 GC 细胞的增殖和侵袭。综上所述,我们的研究表明,circBGN 通过激活 IL6/STAT3 信号通路促进 GC 进展,从而为 GC 提供了一个新的潜在治疗靶点。