Cancer Management and Research (Jan 2021)
Circ_0105346 Knockdown Inhibits Osteosarcoma Development via Regulating miR-1182/WNT7B Axis
Abstract
Jinbao Liu,1 Xiaoyang Li,1 Liang Yue,2 Hao Lv2 1Department of Orthopaedics, The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan 250011, People’s Republic of China; 2Department of Pediatric Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, People’s Republic of ChinaCorrespondence: Hao LvDepartment of Pediatric Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jinshi Road, Lixia District, Jinan 250011, People’s Republic of ChinaTel +86-531-68617091Email [email protected]: Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Circular RNAs (circRNAs) have been reported to affect OS progression. This paper mainly delineated the role of circRNA circ_0105346 in OS development and the potential mechanism.Methods: Quantitative reverse transcription PCR (qRT-PCR) and Western blot assays were applied to detect the expression of circ_0105346, microRNA (miR)-1182 and wingless-type MMTV integration site family 7B (WNT7B). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was conducted to evaluate cell viability, and flow cytometry was performed to monitor cell apoptosis and cycle. In addition, cell migration and invasion were determined via transwell assay. Wound healing assay was also employed to evaluate the migrated capacity of OS cells. Western blot assay was also employed to examine the levels of protein markers. Additionally, the interaction between miR-1182 and circ_0105346 or WNT7B was confirmed by the dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays. Mouse xenograft model was constructed to clarify the effect of circ_0105346 on tumor growth in vivo.Results: Circ_0105346 and WNT7B were upregulated, while miR-1182 was downregulated in OS tissues and cells. Circ_0105346 knockdown suppressed OS cell proliferation, cell cycle, migration, invasion and glycolysis, as well as accelerated apoptosis, which was attenuated by miR-1182 inhibition. Interestingly, circ_0105346 targeted miR-1182, and miR-1182 interacted with WNT7B. Circ_0105346 could upregulate WNT7B by downregulating miR-1182 expression. Furthermore, circ_0105346 knockdown blocked tumor growth in vivo.Conclusion: Circ_0105346 knockdown repressed OS progression by regulating miR-1182/WNT7B axis, at least in part.Keywords: osteosarcoma, circ_0105346, miR-1182, WNT7B, proliferation, apoptosis, metastasis, glycolysis
