Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, P.R.China.
Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, P.R.China.
J Cell Mol Med. 2020 May;24(10):5593-5604. doi: 10.1111/jcmm.15215. Epub 2020 Apr 5.
As a class of covalently closed non-coding RNAs, circular RNAs (circRNAs) are key regulators in various malignancies including osteosarcoma (OS). In the present study, we found that circular RNA PVT1 (circPVT1) was up-regulated in OS and correlated with poor prognosis of patients with OS. Functionally, we showed that knockdown of circPVT1 suppressed OS cells metastasis. In addition, we found that (forkhead box C2) FOXC2 was a downstream gene in circPVT1-mediated metastasis in OS cells. We demonstrated that circPVT1 promoted OS cells metastasis via post-transcriptionally regulating of FOXC2. Furthermore, we revealed that microRNA 526b (miR-526b) was a key bridge which connected circPVT1 and FOXC2. We showed that miR-526b was down-regulated in OS tissue and cell lines. Through a transwell assay, we found that miR-526b suppressed OS cells metastasis by targeting of FOXC2. We also showed that miR-526b targeted circPVT1 via similar mircoRNA response elements (MREs) as it did for FOXC2. Finally, we proved that circPVT1 decoyed miR-526b to promote FOXC2-mediated metastasis in OS cells. In brief, our current study demonstrated that circPVT1, functioning as an oncogene, promotes OS cells metastasis via regulation of FOXC2 by acting as a ceRNA of miR-526b. CircPVT1/miR-526b/FOXC2 axis might be a novel target in molecular treatment of OS.
作为一类共价闭合的非编码 RNA,环状 RNA(circRNA)是包括骨肉瘤(OS)在内的各种恶性肿瘤的关键调节因子。在本研究中,我们发现环状 RNA PVT1(circPVT1)在 OS 中上调,并与 OS 患者的预后不良相关。功能上,我们表明敲低 circPVT1 抑制了 OS 细胞的转移。此外,我们发现(叉头框 C2)FOXC2 是 circPVT1 介导的 OS 细胞转移的下游基因。我们证明 circPVT1 通过转录后调节 FOXC2 促进 OS 细胞转移。此外,我们揭示了 microRNA 526b(miR-526b)是连接 circPVT1 和 FOXC2 的关键桥梁。我们表明 miR-526b 在 OS 组织和细胞系中下调。通过 Transwell 测定,我们发现 miR-526b 通过靶向 FOXC2 抑制 OS 细胞转移。我们还表明,miR-526b 通过与 FOXC2 相似的 mircoRNA 反应元件(MRE)靶向 circPVT1。最后,我们证明 circPVT1 诱饵 miR-526b 促进 OS 细胞中 FOXC2 介导的转移。总之,我们目前的研究表明,circPVT1 作为一种癌基因,通过充当 miR-526b 的 ceRNA 来调节 FOXC2,从而促进 OS 细胞的转移。circPVT1/miR-526b/FOXC2 轴可能是骨肉瘤分子治疗的一个新靶点。