Abstract
BackgroundCircular RNAs (circRNAs) are a new group of non-coding RNAs that play vital roles in cancer occurrence, including gastric cancer (GC). Nevertheless, the role and underlying regulatory mechanisms of circHIPK3 in GC remain unclear.MethodsThe expression levels of circHIPK3, miR-876-5p, and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were estimated by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The proliferation, migration, and invasion of GC cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and transwell assay. Glutaminolysis of GC cells was assessed by measuring glutamine, glutamate, and α-ketoglutarate levels. The western blot was employed to examine the related-protein expression. The association between miR-876-5p and circHIPK3 or PIK3R1 was predicted and affirmed by bioinformatics database starBase v2.0 and dual-luciferase reporter assay, respectively. Eventually, the xenograft experiment was used to assess the role of circHIPK3 silencing in vivo.ResultsCircHIPK3 was upregulated in GC tissues and cells compared with controls, and circHIPK3 was more resistance to RNase R than linear homeodomain interacting protein kinase 3 (HIPK3) mRNA. Silencing of circHIPK3 inhibited GC cells proliferation, migration, invasion, and glutaminolysis as well as tumor tumorigenic ability. Moreover, we also found that miR-876-5p, interacted with PIK3R1, was a target gene of circHIPK3. CircHIPK3 silencing induced effects on GC cells were abolished by silencing of miR-876-5p. In addition, upregulation of PIK3R1 inversed miR-876-5p overexpression-induced effects on GC cells.ConclusionThe circHIPK3 mediated the proliferation, migration, invasion, and glutaminolysis of GC cells partly through regulation of miR-876-5p/PIK3R1 axis by the mechanism of competing endogenous RNAs (ceRNA), indicating circHIPK3 was a GC-associated circRNA that promoted GC development.
Highlights
Circular RNAs are a new group of non-coding RNAs that play vital roles in cancer occurrence, including gastric cancer (GC)
CircHIPK3 was overexpressed in GC tissues and cells Initially, the results of real-time quantitative polymerase chain reaction (RT-qPCR) revealed that circHIPK3 was significantly upregulated in GC tissues and cells compared with neighboring normal tissues and human normal gastric epithelial cell GES-1, respectively (Fig. 1a, b)
Knockdown of circHIPK3 inhibited proliferation, migration, invasion, and glutaminolysis in GC cells As revealed in Fig. 2a, the knockdown experiments were successful using si-circHIPK3 in HGC-27 and AGS cells; the expression of circHIPK3 was decreased after transfection with si-circHIPK3
Summary
Circular RNAs (circRNAs) are a new group of non-coding RNAs that play vital roles in cancer occurrence, including gastric cancer (GC). The role and underlying regulatory mechanisms of circHIPK3 in GC remain unclear. Gastric cancer (GC) is universal malignant tumor all over the world, ranking as the third leading reason of cancerassociated mortality [1]. Numerous studies revealed that circRNAs were closely associated with the occurrence and progress of malignant tumors, including GC. CircHIPK3 was overexpressed in epithelial ovarian cancer, which was associated with poor prognosis of patients [7]. It was uncertain whether circHIPK3 is associated with regulation of GC development
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