Abstract
BackgroundThe aberrant expression of circular RNAs (circRNAs) plays vital roles in the advancement of human cancers, including gastric cancer (GC). In this study, the functions of circRNA ring finger protein 111 (circ-RNF111) in GC were investigated.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circ-RNF111, microRNA-876-3p (miR-876-3p) and krueppel-like factor 12 (KLF12) mRNA. RNase R assay was conducted for the feature of circ-RNF111. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell assay were applied for cell viability, colony formation, migration, and invasion, respectively. Flow cytometry analysis was used to analyze cell apoptosis and cell cycle process. The glycolysis level was examined using specific commercial kits. Western blot assay was carried out to measure the protein levels of hexokinase 2 (HK-2) and KLF12. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the combination between miR-876-3p and circ-RNF111 or KLF12. Murine xenograft model was constructed for the role of circ-RNF111 in vivo. Immunohistochemistry (IHC) was used for KLF12 level.ResultsCirc-RNF111 was higher expressed in GC tissues and cells than normal tissues and cells. Silencing of circ-RNF111 restrained cell viability, colony formation, migration, invasion, cell cycle process and glycolysis and induced apoptosis in GC cells in vitro. Circ-RNF111 positively regulated KLF12 expression via absorbing miR-876-3p. MiR-876-3p downregulation reversed the impacts of circ-RNF111 silencing on GC cell malignant phenotypes. MiR-876-3p overexpression repressed GC cell growth, metastasis and glycolysis, inhibited apoptosis and arrested cell cycle, while KLF12 elevation weakened the effects. Besides, circ-RNF111 knockdown inhibited tumor growth in vivo.ConclusionCirc-RNF111 knockdown relieved the development of GC by regulating miR-876-3p/KLF12 axis.
Highlights
Gastric cancer (GC) is the fourth most usual cancer that endangers human health worldwide [1, 2]
The results exhibited that circ-RNF111 was highly expressed in gastric cancer (GC) tissues compared to adjacent normal tissues (Fig. 1A)
Silencing of circ-RNF111 suppressed the malignant biological behaviors of GC cells To explore the functions of circ-RNF111 in GC, AGS and SNU-638 cells with circ-RNF111 silencing were constructed by transfecting si-circ-RNF111#1 or si-circRNF111#2 into AGS and SNU-638 cells
Summary
Gastric cancer (GC) is the fourth most usual cancer that endangers human health worldwide [1, 2]. Emerging evidence has displayed that circRNAs can act as microRNA (miRNA) sponges to influence gene expression, thereby regulating the biological processes in tumor cells [8, 9]. Circ_0067934 facilitated cell invasion and growth and repressed apoptosis in thyroid cancer by elevating CXCR1 through sponging miR1304 [10]. Circ-ADAM9 aggravated the growth and motility of pancreatic cancer via miR-217/PRSS3 axis [11]. CircRNA ring finger protein 111 (circ-RNF111, hsa_circ_0001982) was identified as an oncogene in breast cancer [15], colorectal cancer [16] as well as GC [17]. The aberrant expression of circular RNAs (circRNAs) plays vital roles in the advancement of human cancers, including gastric cancer (GC). The functions of circRNA ring finger protein 111 (circ-RNF111) in GC were investigated
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