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环状 RNA hsa_circ_0002052 过表达通过调节 miR-1205/APC2 轴抑制 Wnt/β-catenin 通路抑制骨肉瘤进展。

Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis.

机构信息

The Orthopaedic Department of Tongde Hospital of Zhejiang Province, Hangzhou, 310012, PR China.

Department of Pharmacy, Zhejiang Medical & Health Group Hangzhou Hospital, Hangzhou, 310022, PR China.

出版信息

Biochem Biophys Res Commun. 2018 Aug 25;502(4):465-471. doi: 10.1016/j.bbrc.2018.05.184. Epub 2018 Jun 5.

Abstract

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, whose importance in cancer has been gradually acknowledged. However, the functions of circRNAs in tumorigenesis have not been fully understood. In the present study, we identified a novel circRNA hsa_circ_0002052 significantly downregulated in osteosarcoma (OS) tissues and cell lines. Moreover, we found that hsa_circ_0002052 could act as a biomarker to indicate the prognosis of OS patients. Functionally, we showed that hsa_circ_0002052 overexpression significantly suppressed OS cell proliferation, migration and invasion while promoting apoptosis in vitro. Similarly, in vivo assay indicated that ectopic expression of hsa_circ_0002052 impaired OS cell growth. In terms of mechanism, we found that hsa_circ_0002052 inhibited miR-1205 while miR1205 targeted APC2, a negative regulator of Wnt/β-catenin signaling pathway. By releasing the inhibition of miR-1205 on APC2 expression, hsa_circ_0002052 suppressed the activation of Wnt/β-catenin signaling pathway, leading to attenuated OS progression. Taken together, our study for the first time revealed a suppressive circRNA hsa_circ_0002052 involved in OS progression. Our study suggested hsa_circ_0002052/miR-1205/APC2/Wnt/β-catenin axis might be a potential target for OS therapy.

摘要

环状 RNA(circRNAs)是一类新型的非编码 RNA,其在癌症中的重要性逐渐得到认可。然而,circRNAs 在肿瘤发生中的功能尚未完全理解。在本研究中,我们鉴定出一种在骨肉瘤(OS)组织和细胞系中显著下调的新型环状 RNA hsa_circ_0002052。此外,我们发现 hsa_circ_0002052 可以作为 OS 患者预后的生物标志物。功能上,我们表明 hsa_circ_0002052 过表达可显著抑制 OS 细胞的增殖、迁移和侵袭,同时促进体外细胞凋亡。同样,体内实验表明 hsa_circ_0002052 的异位表达可损害 OS 细胞的生长。在机制方面,我们发现 hsa_circ_0002052 抑制了 miR-1205,而 miR1205 靶向 APC2,后者是 Wnt/β-catenin 信号通路的负调节剂。通过释放对 APC2 表达的 miR-1205 抑制,hsa_circ_0002052 抑制了 Wnt/β-catenin 信号通路的激活,导致 OS 进展减弱。总之,我们的研究首次揭示了参与 OS 进展的抑制性环状 RNA hsa_circ_0002052。我们的研究表明 hsa_circ_0002052/miR-1205/APC2/Wnt/β-catenin 轴可能是 OS 治疗的潜在靶点。

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