| Summary: | Zheng Liu,1,* Ronghai Wang,2,* Guangze Zhu3 1Department of Traditional Chinese Medicine and Acupuncture, Central Hospital of Baoji, Baoji City, Shaanxi Province, People’s Republic of China; 2Department of Urology, Linzi District People’s Hospital, Zibo City, Shandong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun City, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangze ZhuDepartment of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun, Jilin Province 130021, People’s Republic of ChinaTel/Fax +86 431-86177939Email zhugz0820@126.comBackground: Renal cell carcinoma (RCC) that originates from the proximal renal tubules is the most common cancer of the human kidney. Increasing circRNA/miRNA/mRNA networks have been found in RCC regulation. This study will explore the regulatory relation of circular RNA (circRNA) circ_0035483, microRNA-31-5p (miR-31-5p) and high mobility group A1 (HMGA1).Methods: The levels of circ_0035483, miR-31-5p and HMGA1 were measured by real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation was determined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were assessed by transwell assay. HMGA1 and epithelial–mesenchymal transition (EMT)-related protein levels were quantified using Western blot. Glycolytic metabolism was evaluated by glucose consumption and lactate production. The interaction between targets was confirmed via dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo experiment was performed through the establishment of xenograft models in mice.Results: Circ_0035483 expression was upregulated in RCC tissues and cells. The inhibitory effects on RCC cell proliferation, migration, invasion, EMT and glycolysis were induced after circ_0035483 was downregulated. MiR-31-5p was identified as a target of circ_0035483 and miR-31-5p upregulation was related to the function of circ_0035483 knockdown in RCC cells. Additionally, miR-31-5p targeted HMGA1 and inhibited the malignant behaviors of RCC cells by negatively regulating HMGA1. Moreover, HMGA1 expression was regulated by circ_0035483 via targeting miR-31-5p. Circ_0035483 also affected tumor growth in vivo by relying on the miR-31-5p/HMGA1 axis.Conclusion: These findings clarified that the tumor-promoting function of circ_0035483 in RCC was partly achieved by regulating the miR-31-5p/HMGA1 axis.Keywords: circ_0035483, renal cell carcinoma; RCC, miR-31-5p, HMGA1
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