PMID- 33472586 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20240226 IS - 2661-8850 (Electronic) IS - 2661-8850 (Linking) VI - 22 IP - 1 DP - 2021 Jan 20 TI - circRNA_0005529 facilitates growth and metastasis of gastric cancer via regulating miR-527/Sp1 axis. PG - 6 LID - 10.1186/s12860-020-00340-8 [doi] LID - 6 AB - BACKGROUND: Circular RNAs (circRNAs) are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA (miRNA) interaction, protein binding and regulatory splicing. circRNA_0005529 (circ_0005529) is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined. In this study, the expression and location of circ_0005529 and microRNA-527 (miR-527) were determined by qRT-PCR and fluorescence in situ hybridization (FISH). Cell proliferation and cell migration were determined by MTT, EdU incorporation, colony formation, wound scratch and transwell assays. In addition, immunohistochemistry and western blotting were performed to determine the expressions of specificity protein 1 (Sp1), PCNA, c-myc, E-cadherin and N-cadherin. Western blotting and luciferase reporter assay were performed to study the interaction between circ_0005529 and miR-527 or miR-527 and Sp1. The functional effects of circ_0005529 on GC through regulating Sp1 were further evaluated using xenograft and metastatic mouse models in vivo. RESULTS: Our results showed that circ_0005529 was upregulated in GC tissues and cells, and had promoting effects on cell proliferation and cell migration. Mechanism analysis suggested that circ_0005529 could bind to microRNA-527 (miR-527) and reduce its expression. The interaction between miR-527 and Sp1 in GC was systematically studied. In addition, the results indicated that Sp1 upregulation could rescue the effects on cell proliferation and migration caused by circ_0005529. Moreover, the inhibitory effects of circ_0005529 downregulation on GC growth and metastasis were evaluated in mouse models. These findings suggested that the axis of circ_0005529/miR-527/Sp1 may serve as a promising treatment target for GC diagnosis and treatment. CONCLUSIONS: These findings suggested that the signal axis of circ_0005529/miR-527/Sp1 may has the potential to be explored as a novel therapeutic target for GC diagnosis and treatment. Mechanism diagram: During GC development, overexpressed circ_0005529 sponged miR-527 and then upregulated the expression of Sp1. Subsequently, epithelial-mesenchymal transition (EMT), cell proliferation and cell migration were promoted, which ultimately facilitated the tumor metastasis. FAU - Zhang, Xing AU - Zhang X AD - Department of Gastrointestinal Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Yang, Hongwei AU - Yang H AD - Department of Breast and Thyroid Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Jia, Yingdong AU - Jia Y AD - Department of Gastrointestinal Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Xu, Zhengwen AU - Xu Z AD - Department of Gastrointestinal Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Zhang, Liuping AU - Zhang L AD - Department of Gastrointestinal Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Sun, Meng AU - Sun M AD - Department of Gastrointestinal Surgery, Suining Central Hospital, Suining City, 629000, Sichuan Province, China. FAU - Fu, Jing AU - Fu J AUID- ORCID: 0000-0001-7887-0266 AD - Department of Emergency, Huai'an Hospital Affiliated of Xuzhou Medical University and Huai'an Second People's Hospital, No. 62 Huaihai South Road, Huai 'an City, Jiangsu Province, China. GHUI6trf89@163.com. LA - eng GR - 130493/Scientific Research Task of Sichuan Provincial Health Department/ PT - Journal Article DEP - 20210120 PL - England TA - BMC Mol Cell Biol JT - BMC molecular and cell biology JID - 101741148 RN - 0 (3' Untranslated Regions) RN - 0 (MIRN527 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (Sp1 Transcription Factor) SB - IM MH - 3' Untranslated Regions/genetics MH - Aged MH - Animals MH - Base Sequence MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/*genetics/metabolism MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - RNA, Circular/genetics/*metabolism MH - Sp1 Transcription Factor/*genetics MH - Stomach Neoplasms/genetics MH - Up-Regulation/genetics MH - Mice PMC - PMC7816457 OTO - NOTNLM OT - Cell migration OT - Cell proliferation OT - Gastric cancer OT - Sp1 OT - circ_0005529 OT - miR-527 COIS- The authors state that there are no conflicts of interest to disclose. EDAT- 2021/01/22 06:00 MHDA- 2021/08/27 06:00 PMCR- 2021/01/20 CRDT- 2021/01/21 05:24 PHST- 2020/07/01 00:00 [received] PHST- 2020/12/22 00:00 [accepted] PHST- 2021/01/21 05:24 [entrez] PHST- 2021/01/22 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] PHST- 2021/01/20 00:00 [pmc-release] AID - 10.1186/s12860-020-00340-8 [pii] AID - 340 [pii] AID - 10.1186/s12860-020-00340-8 [doi] PST - epublish SO - BMC Mol Cell Biol. 2021 Jan 20;22(1):6. doi: 10.1186/s12860-020-00340-8.