PMID- 36643863 OWN - NLM STAT- MEDLINE DCOM- 20230118 LR - 20230118 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 18 DP - 2023 TI - Exosome-Delivered circSTAU2 Inhibits the Progression of Gastric Cancer by Targeting the miR-589/CAPZA1 Axis. PG - 127-142 LID - 10.2147/IJN.S391872 [doi] AB - BACKGROUND: Circular RNAs (circRNAs) are endogenous noncoding RNAs that play vital roles in many biological processes, particularly in human cancer. Recent studies indicate that circRNAs play an important role in tumor progression through exosomes. However, the specific functions of gastric cancer-derived exosomes and the role of circSTAU2 in gastric cancer (GC) remain largely unknown. METHODS: Differentially expressed circRNAs in GC were identified by circRNA microarrays analysis and quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSTAU2 in GC was verified by circSTAU2 knockdown and overexpression with functional assays both in vitro and in vivo. Fluorescence in situ hybridization (FISH), immunofluorescence, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, qRT-PCR and Western blot were adopted to evaluate the expression and regulatory mechanism of MBNL1, circSTAU2, miR-589 and CAPZA1. Furthermore, the role of exosomes was demonstrated by transmission electron microscopy and nano-sight particle tracking analysis. RESULTS: CircSTAU2, mainly localized in the cytoplasm, was significantly downregulated in GC. CircSTAU2 overexpression inhibited GC cell proliferation, invasion and migration both in vitro and in vivo, while circSTAU2 knockdown had the inverse effect. CircSTAU2 could be wrapped in exosomes and delivered to recipient cells, and functioned as a sponge for miR-589 to relieve its inhibitory effect on CAPZA1, thus inhibiting GC progression. Furthermore, MBNL1 acted as the upstream RNA-binding protein of circSTAU2 and significantly influenced the circularization and expression of circSTAU2. CONCLUSION: Exosome-delivered circSTAU2 may act as a tumor suppressor that restrains GC progression via miR-589/CAPZA1 axis, which demonstrates a potential therapeutic target for GC. CI - (c) 2023 Zhang et al. FAU - Zhang, Chenggang AU - Zhang C AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Wei, Guanxin AU - Wei G AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Zhu, Xiuxian AU - Zhu X AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Chen, Xiang AU - Chen X AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Ma, Xianxiong AU - Ma X AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Hu, Peng AU - Hu P AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Liu, Weizhen AU - Liu W AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Yang, Wenchang AU - Yang W AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Ruan, Tuo AU - Ruan T AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Zhang, Weikang AU - Zhang W AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Wu, Chuanqing AU - Wu C AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Tao, Kaixiong AU - Tao K AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. LA - eng PT - Journal Article DEP - 20230106 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (CapZ Actin Capping Protein) RN - 0 (CAPZA1 protein, human) RN - 0 (MicroRNAs) RN - 0 (MIRN589 microRNA, human) RN - 0 (RNA, Circular) RN - 0 (STAU2 protein, human) SB - IM MH - Humans MH - CapZ Actin Capping Protein/genetics/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - *Exosomes/metabolism MH - Gene Expression Regulation, Neoplastic MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/genetics/metabolism MH - *RNA, Circular/genetics/metabolism MH - *Stomach Neoplasms/pathology PMC - PMC9832994 OTO - NOTNLM OT - bioinformatics OT - cancer progression OT - circ-RNAs OT - exosomes OT - gastric cancer COIS- The authors report no conflicts of interest in this work. EDAT- 2023/01/17 06:00 MHDA- 2023/01/18 06:00 PMCR- 2023/01/06 CRDT- 2023/01/16 02:49 PHST- 2022/10/07 00:00 [received] PHST- 2022/12/22 00:00 [accepted] PHST- 2023/01/16 02:49 [entrez] PHST- 2023/01/17 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] PHST- 2023/01/06 00:00 [pmc-release] AID - 391872 [pii] AID - 10.2147/IJN.S391872 [doi] PST - epublish SO - Int J Nanomedicine. 2023 Jan 6;18:127-142. doi: 10.2147/IJN.S391872. eCollection 2023.