The 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. Quantitative 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. Circ-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. Circ-RNF111 knockdown relieved the development of GC by regulating miR-876-3p/KLF12 axis.

中文翻译：

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Circ-RNF111 通过 miR-876-3p 依赖性调控 KLF12 加重胃癌的恶性程度

环状 RNA (circRNA) 的异常表达在包括胃癌 (GC) 在内的人类癌症的进展中起着至关重要的作用。在本研究中，研究了 circRNA 无名指蛋白 111 (circ-RNF111) 在 GC 中的功能。对 circ-RNF111、microRNA-876-3p (miR-876-3p) 和 krueppel 样因子 12 (KLF12) mRNA 水平进行定量实时聚合酶链反应 (qRT-PCR) 测定。对 circ-RNF111 的特征进行了 RNase R 检测。Cell Counting Kit-8 (CCK-8) 试验、集落形成试验、伤口愈合试验和 transwell 试验分别用于细胞活力、集落形成、迁移和侵袭。流式细胞仪分析用于分析细胞凋亡和细胞周期过程。使用特定的商业试剂盒检查糖酵解水平。进行蛋白质印迹测定以测量己糖激酶2（HK-2）和KLF12的蛋白质水平。采用双荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定来验证 miR-876-3p 与 circ-RNF111 或 KLF12 之间的组合。构建了小鼠异种移植模型，用于体内 circ-RNF111 的作用。免疫组织化学 (IHC) 用于 KLF12 水平。Circ-RNF111在GC组织和细胞中的表达高于正常组织和细胞。circ-RNF111的沉默抑制了体外GC细胞的细胞活力、集落形成、迁移、侵袭、细胞周期过程和糖酵解，并诱导了细胞凋亡。Circ-RNF111 通过吸收 miR-876-3p 正向调节 KLF12 的表达。MiR-876-3p 下调逆转了 circ-RNF111 沉默对 GC 细胞恶性表型的影响。MiR-876-3p 过表达抑制 GC 细胞生长、转移和糖酵解，抑制细胞凋亡和停滞细胞周期，而 KLF12 升高减弱了这些作用。此外，circ-RNF111 敲低可抑制体内肿瘤生长。Circ-RNF111 敲低通过调节 miR-876-3p/KLF12 轴缓解了 GC 的发展。