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长链非编码 RNA HNF1A-AS1 是骨肉瘤的一个负预后因子,并促进肿瘤发生。

The lncRNA HNF1A-AS1 is a negative prognostic factor and promotes tumorigenesis in osteosarcoma.

机构信息

Department of Orthopedics, the First Affiliated Hospital, Soochow University, Suzhou, China.

Department of Orthopedics, Ningxia People's Hospital, Yingchuan, Ningxia, China.

出版信息

J Cell Mol Med. 2017 Nov;21(11):2654-2662. doi: 10.1111/jcmm.12944. Epub 2017 Sep 2.

Abstract

Recent studies have revealed that long noncoding RNA HNF1A-antisense 1 (HNF1A-AS1) plays an important role in the development of several human malignancy entities. However, the expression and function of HNF1A-AS1 in the carcinogenesis and development of osteosarcoma remains unknown. In this study, we detected the HNF1A-AS1 levels in human osteosarcoma tissues and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and investigated its role in osteosarcoma by using in vitro assays. Our study showed that HNF1A-AS1 expression was significantly up-regulated in human osteosarcoma tissues and cell lines compared with their normal counterparts, and its expression level was positively correlated with the distance metastasis (P = 0.009) and tumour stage (P = 0.019). Moreover, Kaplan-Meier curves with the log-rank test showed that higher expression of HNF1A-AS1 conferred a significantly poorer survival and multivariate Cox proportional hazards analysis revealed that HNF1A-AS1 was an independent risk factor of overall survival. In addition, the expression of HNF1A-AS1 in serum is correlated with patients' status and receiver operating characteristic (ROC) curve analysis demonstrated that HNF1A-AS1 could distinguish patients with osteosarcoma from healthy individuals (the area under curve 0.849, P < 0.001). Furthermore, in vitro knockdown of HNF1A-AS1 by siRNA significantly inhibited cell proliferation and G /S transition, and suppressed migration and invasion by reducing the epithelial-mesenchymal transition (EMT) program in osteosarcoma cells. Taken together, our data suggested that HNF1A-AS1 is a novel molecule involved in osteosarcoma progression, which may provide as a potential diagnostic, prognostic biomarker and therapeutic target.

摘要

最近的研究表明,长链非编码 RNA HNF1A-反义 1(HNF1A-AS1)在几种人类恶性实体的发展中发挥着重要作用。然而,HNF1A-AS1 在骨肉瘤的发生和发展中的表达和功能尚不清楚。在本研究中,我们通过实时定量聚合酶链反应(qRT-PCR)检测了人骨肉瘤组织和细胞系中的 HNF1A-AS1 水平,并通过体外实验研究了其在骨肉瘤中的作用。我们的研究表明,与正常组织相比,HNF1A-AS1 在人骨肉瘤组织和细胞系中的表达显著上调,并且其表达水平与远处转移(P = 0.009)和肿瘤分期(P = 0.019)呈正相关。此外,对数秩检验的 Kaplan-Meier 曲线表明,HNF1A-AS1 表达较高的患者生存明显较差,多因素 Cox 比例风险分析表明 HNF1A-AS1 是总生存期的独立危险因素。此外,HNF1A-AS1 在血清中的表达与患者的状态相关,受试者工作特征(ROC)曲线分析表明 HNF1A-AS1 能够区分骨肉瘤患者与健康个体(曲线下面积 0.849,P < 0.001)。此外,通过 siRNA 敲低 HNF1A-AS1 可显著抑制骨肉瘤细胞的增殖和 G1/S 期转换,并通过减少上皮-间充质转化(EMT)程序来抑制迁移和侵袭。综上所述,我们的数据表明 HNF1A-AS1 是参与骨肉瘤进展的新型分子,它可能作为一种潜在的诊断、预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaea/5661255/bea9ff05c945/JCMM-21-2654-g001.jpg

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