Abstract
BackgroundEndometrial cancer (EC) is a common malignancy of the female reproductive system. Circular RNAs (circRNAs) were demonstrated to exert critical roles in cancers, including EC. This study aimed to investigate the effects of hsa_circRNA_0001776 (circ_0001776) on EC.MethodsReal-time quantitative PCR (RT-qPCR) was used to measure circ_0001776, microRNA-182 (miR-182) and leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) expression. The diagnostic and prognostic values of circ_0001776 were identified by receiver operating characteristic (ROC) curve analysis and survival analysis, respectively. RNase R digestion was used to characterize circ_0001776, and the localization of circ_0001776 was evaluated by cell fractionation assay. Then, cell counting kit-8 (CCK-8), colony formation, and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. The real-time glycolytic rate (ECAR) and lactate production were measured by extracellular flux analysis and a lactate assay kit, respectively. Bioinformatics analysis and dual-luciferase reporter assay were used to determine the interaction among circ_0001776, miR-182 and LRIG2. The protein expression of LRIG2 was determined by western blot. Moreover, circ_0001776 overexpression vector was used to upregulate circ_0001776 expression in an animal tumor model.ResultsCirc_0001776 and LRIG2 were downregulated, while miR-182 was upregulated in EC tissues and cells. Low expression of circ_0001776 was correlated with the 5-year survival rate of EC patients. Upregulated circ_0001776 markedly attenuated cell proliferation and glycolysis, and enhanced cell apoptosis. Besides, circ_0001776 sponged miR-182 to regulate LRIG2 expression. Circ_0001776 could suppress EC progression by miR-182/LRIG2 axis. Furthermore, we also found that circ_0001776 significantly inhibited tumor growth in vivo.ConclusionOur results confirmed that circ_0001776 inhibited EC tumorigenesis and progression via miR-182/LRIG2 axis, providing a potential therapeutic target for EC.
Highlights
Endometrial cancer (EC) is a common malignancy of the female reproductive system
EC is conventionally classified into type I EC and type II EC according to molecular genetic features and clinicopathological features, and grades 1 and 2 are regarded as “type I”, while grade 3 is regarded as “type II” [2, 3]
CircInteractome showed that miR-182 might be a target of circ_0001776, we aimed to explore the functional effects of circ_0001776 and miR-182 on EC tumorigenesis
Summary
Endometrial cancer (EC) is a common malignancy of the female reproductive system. This study aimed to investigate the effects of hsa_circRNA_0001776 (circ_0001776) on EC. Endometrial cancer (EC), mainly occurred in postmenopausal women, is one of the most common malignancies of the female reproductive system with the incidence of about 1/10,000 in worldwide [1]. The prognosis of “type I” EC patients was relatively favorable, while “type II” EC was always accompanied by the poor outcomes. Several circRNAs were confirmed to be the ideal biomarkers for the diagnosis, treatment, and prognosis of various human cancers [9, 10]. Hsa_circ_0052112 could regulate breast cancer tumorigenesis through facilitating cell metastasis [11]. Hsa_circRNA_0001776 (circ_0001776) was downregulated in EC tissues [12]. The regulatory effects of circ_0001776 in EC remain largely unknown and the underlying mechanisms need further understanding
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