Tohoku J. Exp. Med., 2021 July, 254(3)

Circular RNA circ_0046264 Suppresses Osteosarcoma Progression via microRNA-940/Secreted Frizzled Related Protein 1 Axis

Rui Du,1 Bingjin Fu,1 Guangchao Sun,1 Bingdong Ma,2 Mingming Deng,1 Xiaodong Zhu1 and Dehai Kong1

1Department of Foot and Ankle Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China
2Department of Foot and Ankle Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

Circular RNAs (circRNAs) feature prominently in regulating tumor progression. The study aims to investigate the role and mechanism of circ_0046264 in osteosarcoma. In this study, dysregulated circRNAs in osteosarcoma tissues and adjacent tissues were screened out by analyzing circRNA microarray (GSE140256). The expressions of circ_0046264 in 58 osteosarcoma tissues and 4 osteosarcoma cell lines were detected by quantitative real-time polymerase chain reaction. Subsequently, the relationship of circ_0046264 expression level and clinical features were analyzed. Ethyldeoxyuridine assay and Transwell assay were employed to detect cell viability, migration and invasion. Dual-luciferase reporter assay was adopted to confirm the targeting relationships between circ_0046264 and microRNA-940 (miR-940), as well as miR-940 and secreted frizzled related protein 1 (SFRP1). SFRP1 expression was determined by western blot. Here, we demonstrated that circ_0046264 was greatly down-regulated in osteosarcoma and was inversely related to tumor size and Ki67 expression. Functional assays validated that circ_0046264 could restrain the proliferation, migration and invasion. Mechanistically, circ_0046264 could adsorb miR-940 and indirectly modulate SFRP1 expression. Furthermore, the transfection of miR-940 mimics or SFRP1 small interfering RNA could reverse the impact of circ_0046264 overexpression on the growth, migration and invasion of osteosarcoma cells. Taken together, circ_0046264 is a tumor suppressor to inhibit the osteosarcoma progression via modulating the miR-940 / SFRP1 axis.

Key words —— circ_0046264; microRNA-940; migration; osteosarcoma; secreted frizzled related protein 1

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Tohoku J. Exp. Med 2021, 254, 189-197.

Correspondence: Dehai Kong, Department of Foot and Ankle Surgery, Affiliated Hospital of Binzhou Medical University, No. 661, Huanghe 2nd Road, Binzhou, Shandong 256600, China.

e-mail: kongdh2010@163.com