Abstract
BackgroundCircular 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.ResultsOur 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.ConclusionsThese 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.Graphical abstractMechanism 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
Highlights
Circular RNAs are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA interaction, protein binding and regulatory splicing. circRNA_0005529 is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined
Through high-throughput sequencing and bioinformatics analysis, more and more circRNAs are identified in GC. circRNA_0005529, derived from alternative splicing of vacuolar protein sorting 33B (VPS33B) transcript, was recently demonstrated to be upregulated in GC tissues based on circRNA chip profiles (GSE78092) [9]
As a member of the Sp/KLF family, the transcription factor specificity protein 1 (Sp1) is involved in regulating the expression of genes related to tumor progression-related signal pathways [13, 14]
Summary
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. 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. MiR-527 was identified to suppress lung cancer cell proliferation and migration through targeting TFIIBrelated factor 2 (BRF2), an oncogene that is critical for Pol III recruitment and transcription initiation [12]. These findings showed that miR-527 may exert different functions in various tumors. Given the apparent overexpression of Sp1, a better insight into the function and underlying mechanism of Sp1 in GC is needed
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