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长链非编码RNA PCAT-1通过降低p21水平在骨肉瘤中发挥癌基因作用。

Long noncoding RNA PCAT-1 acts as an oncogene in osteosarcoma by reducing p21 levels.

作者信息

Huang Jiang, Deng Gaorong, Liu Tianmi, Chen Wenzhao, Zhou Yang

机构信息

Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yong Waizheng Street, Nanchang 330006, China.

Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of Nanchang University, Nanchang 330009, China.

出版信息

Biochem Biophys Res Commun. 2018 Jan 22;495(4):2622-2629. doi: 10.1016/j.bbrc.2017.12.157. Epub 2017 Dec 29.

Abstract

Long non-coding RNA (lncRNA) is emerging as a critical regulator in multiple cancers. Recently, lncRNA PCAT-1 was found to be up-regulated in prostate cancer and hepatocellular carcinoma, exerting oncogenic effects. However, the biological function and regulatory mechanism of PCAT-1 remain unclear in osteosarcoma (OS). In this study, we reported that PCAT-1 expression was also upregulated in OS tissues, and its overexpression was remarkably associated with tumor size, Enneking stage, tumor node metastasis (TNM) stage and metastasis in patients with OS. Knockdown of PCAT-1 suppressed OS cells proliferation, migration and invasion in vitro, and inhibited the tumorigenicity of OS cells in vivo. Mechanistic investigations revealed that PCAT-1 could interact with EZH2, thereby repressing p21 expression. Additionally, rescue experiments indicated that PCAT-1 functioned as an oncogene partly via suppressing p21 in OS cells. Collectively, our findings demonstrate that PCAT-1 is a new candidate for use in OS diagnosis, prognosis and therapy.

摘要

长链非编码RNA(lncRNA)正成为多种癌症中的关键调节因子。最近,发现lncRNA PCAT-1在前列腺癌和肝细胞癌中上调,发挥致癌作用。然而,PCAT-1在骨肉瘤(OS)中的生物学功能和调控机制仍不清楚。在本研究中,我们报道PCAT-1在OS组织中也上调,其过表达与OS患者的肿瘤大小、Enneking分期、肿瘤淋巴结转移(TNM)分期及转移显著相关。敲低PCAT-1可抑制OS细胞在体外的增殖、迁移和侵袭,并在体内抑制OS细胞的致瘤性。机制研究表明,PCAT-1可与EZH2相互作用,从而抑制p21表达。此外,挽救实验表明,PCAT-1在OS细胞中部分通过抑制p21发挥癌基因作用。总体而言,我们的研究结果表明,PCAT-1是用于OS诊断、预后和治疗的新候选物。

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