CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182

Abstract

Background Endometrial 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. Methods Real-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. Results Circ_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. Conclusion Our results confirmed that circ_0001776 inhibited EC tumorigenesis and progression via miR-182/LRIG2 axis, providing a potential therapeutic target for EC.

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

“…Similarly, Jia et al reported that LRIG2, a tumor suppressor gene mainly expressed in the ovaries and uterus, contain a putative binding site for miR-182 [140]. As a result, overexpression of miR-182 in EC overrides the inhibitory effects of LRIG2 on cell growth and the glycolytic metabolism [47].…”

Circular RNAs: A Promising Biomarker for Endometrial Cancer

“…In addition, circ_0001776 also regulated the expression of LRIG2 by acting as a sponge for miR-182, and CIRC_0001776 inhibited EC progression through miR-182/LRIG2 axis. 11 , 131 …”

“…In other words, circ_0001776 inhibits the occurrence and development of EC through miR-182/LRIG2 axis, providing a potential target for the treatment of EC. 131 …”

circ‑ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR‑582‑5p/ERO1A signaling axis

“…Circular RNAs (circRNAs/circ), a novel class of non-coding RNAs (ncRNAs), are characterized by a covalently closed loop without a 5 cap and 3 polyadenylated tail, and are generated through abnormal transcription and splicing ( 6 ). Accumulating evidence has demonstrated that circRNAs exert effects on multiple biological and pathological processes, suggesting that they may be involved in the occurrence and development of numerous diseases, including cancer ( 7 , 8 ). For example, circ-acetyl-CoA carboxylase α (ACACA) has been previously reported to promote the proliferation of non-small cell lung cancer (NSCLC) cells by modulating proliferation, migration and glycolysis via microRNA (miRNA/miR)-1183 and the PI3K/AKT signaling pathway ( 9 ).…”