Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR-326/IGF1R axis
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Cancer Cell International Open Access
PRIMARY RESEARCH
Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR‑326/IGF1R axis Shuwei He, Jianzeng Yang, Shitao Jiang, Yuan Li and Xingmin Han*
Abstract Background: Circular RNAs (circRNAs) play vital roles in hepatocellular carcinoma development. However, the role and mechanism of circRNA hsa_circ_0000517 (circ_0000517) in hepatocellular carcinoma development were largely unknown. Methods: 45 paired tumor and adjacent nontumor samples were collected from hepatocellular carcinoma patients. The levels of circ_0000517, miR-326 and insulin-like growth factor type 1 receptor (IGF1R) were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, colony ability, migration, invasion and glycolysis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, western blot, transwell assay, glucose consumption, lactate production or adenosine triphosphate (ATP) production. The target correlation between miR-326 and circ_0000517 or IGF1R was analyzed via dual-luciferase reporter analysis. The function of circ_0000517 in vivo was assessed via xenograft model. Results: circ_0000517 expression was elevated in hepatocellular carcinoma tissues and cell lines. circ_0000517 knockdown suppressed cell viability, colony formation, migration, invasion and glycolysis. miR-326 was sponged via circ_0000517 and miR-326 knockdown reversed the effect of circ_0000517 silence on hepatocellular carcinoma development. miR-326 overexpression inhibited hepatocellular carcinoma development through targeting IGF1R. circ_0000517 knockdown decreased IGF1R expression by modulating miR-326. circ_0000517 downregulation reduced xenograft tumor growth. Conclusion: circ_0000517 knockdown repressed hepatocellular carcinoma development in vitro and in vivo by modulating miR-326 and IGF1R. Keywords: Hepatocellular carcinoma, circ_0000517, miR-326, IGF1R Background Liver cancer is one of the main causes of cancer-associated death with rising incidence and mortality [1]. Hepatocellular carcinoma accounts for majority of liver cancer [2]. Improvements have been gained in prevention and management of hepatocellular carcinoma [3]. *Correspondence: [email protected] Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou 450000, Henan, China
Nevertheless, some patients have poor prognosis. To improve the treatment and prognosis of hepatocellular carcinoma, the mechanism modulating the progression of hepatocellular carcinoma is sorely wanted. Circular RNAs (circRNAs) are a group of noncoding RNAs generated via covalently linking the 5′ cap and 3′ end [4]. Many circRNAs are ubiquitously expressed in eukaryotes [5]. Moreover, circRNAs play essential roles in development and treatment of cancers [6]. The emerging evidence demonstrates that circRNAs have pivotal roles in diagnosis and therapy of hepatocellular
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