Circ_0003732 promotes osteosarcoma progression through regulating miR-377-3p/CPEB1 axis and Wnt/β-catenin signaling pathway

骨肉瘤 Wnt信号通路 癌症研究 细胞生长 化学 癌变 基因敲除 肿瘤进展 流式细胞术 细胞凋亡 连环素 信号转导 分子生物学 生物 癌症 遗传学 生物化学
作者
Zheng Zhou,Tang Liu,Zhihong Li,Lu Wang
出处
期刊:Anti-Cancer Drugs [Ovid Technologies (Wolters Kluwer)]
卷期号:33 (1): e299-e310 被引量:9
标识
DOI:10.1097/cad.0000000000001206
摘要

Osteosarcoma is a prevalent malignant bone cancer. This study aimed to explore the biologic role and potential mechanism of circ_0003732 in osteosarcoma carcinogenesis. Quantitative real-time PCR was implemented to detect the RNA expression of circ_0003732, microRNA-377-3p (miR-377-3p) and cytoplasmic polyadenylation element-binding protein 1 (CPEB1). Cell proliferation was evaluated by cell counting kit-8 assay and colony formation assay. Transwell, wound healing and flow cytometry assays were employed to assess cell migration, invasion and apoptosis. In addition, the interaction between miR-377-3p and circ_0003732 or CPEB1 was validated by dual-luciferase reporter assay. The protein expression was detected by western blot assay or immunohistochemistry assay. Xenograft tumor assay was performed to explore the regulation of circ_0003732 on osteosarcoma tumor growth in vivo. Circ_0003732 was upregulated in osteosarcoma tissues and cells. Knockdown of circ_0003732 suppressed osteosarcoma cell proliferation, migration, invasion and triggered cell apoptosis in vitro, as well as reduced osteosarcoma tumor growth in vivo. Meanwhile, miR-377-3p could bind to circ_0003732 and CPEB1 and miR-377-3p inhibitor could reverse the effects of circ_0003732 silence on osteosarcoma cell progression. Furthermore, CPEB1 overexpression could overturn the suppressive impacts of miR-377-3p on osteosarcoma progression. In addition, circ_0003732 silence restrained Wnt/β-catenin signaling pathway via regulating miR-377-3p in osteosarcoma cells. Circ_0003732 might play a positive role in the malignant progression of osteosarcoma by regulating the miR-377-3p/CPEB1 axis and activating the Wnt/β-catenin signaling pathway, which might provide new insights for osteosarcoma therapy.
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