Shi Hao, Huang Shan, Qin Mingde, Xue Xiaofeng, Guo Xingpo, Jiang Linhua, Hong Han, Fang Jian, Gao Ling
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Front Cell Dev Biol. 2021 May 26;9:676319. doi: 10.3389/fcell.2021.676319. eCollection 2021.
Cancer-associated fibroblast (CAF)-derived exosomes play a major role in gastric carcinoma (GC) tumorigenesis. However, the mechanism behind the activity of circular RNAs in CAF-derived exosomes in GC remains unclear. In the present study, we identified differentially expressed circ_0088300 in GC tissues and plasma exosomes. We found that CAFs delivered functional circ_0088300 to GC tumor cells via exosomes and promoted the proliferation, migration and invasion abilities of GC cells. Furthermore, we demonstrated that circ_0088300 packaging into exosomes was driven by KHDRBS3. In addition, we verified that circ_0088300 served as a sponge that directly targeted miR-1305 and promoted GC cell proliferation, migration and invasion. Finally, the JAK/STAT signaling pathway was found to be involved in the circ_0088300/miR-1305 axis, which accelerates GC tumorigenesis. In conclusion, our results indicated a previously unknown regulatory pathway in which exosomal circ_0088300 derived from CAFs acts as a sponge of miR-1305 and promotes GC cell proliferation, migration and invasion; these data identify a potential biomarker and novel therapeutic target for GC in the future.
癌症相关成纤维细胞(CAF)衍生的外泌体在胃癌(GC)肿瘤发生中起主要作用。然而,GC中CAF衍生的外泌体中环状RNA活性背后的机制仍不清楚。在本研究中,我们鉴定了GC组织和血浆外泌体中差异表达的circ_0088300。我们发现CAF通过外泌体将功能性circ_0088300递送至GC肿瘤细胞,并促进GC细胞的增殖、迁移和侵袭能力。此外,我们证明circ_0088300包装到外泌体中是由KHDRBS3驱动的。另外,我们证实circ_0088300作为一种海绵,直接靶向miR-1305并促进GC细胞增殖、迁移和侵袭。最后,发现JAK/STAT信号通路参与circ_0088300/miR-1305轴,加速GC肿瘤发生。总之,我们的结果表明了一种先前未知的调节途径,其中源自CAF的外泌体circ_0088300充当miR-1305的海绵并促进GC细胞增殖、迁移和侵袭;这些数据确定了未来GC的潜在生物标志物和新的治疗靶点。