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长链非编码RNA HOTTIP在骨肉瘤患者中上调并与不良预后相关。

Long non-coding RNA HOTTIP is up-regulated and associated with poor prognosis in patients with osteosarcoma.

作者信息

Li Fan, Cao Lei, Hang Donghua, Wang Fang, Wang Qiugen

机构信息

Department of Trauma and Orthopedics, Trauma Emergency Center, Shanghai First People's Hospital, Shanghai Jiao Tong University Shanghai 200011, China.

出版信息

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11414-20. eCollection 2015.

PMID:26617868
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4637684/
Abstract

Long non-coding RNAs (lncRNAs) have been shown to play key roles in cancer development and progression. In this study, we focused on lncRNA HOTTIP and investigated its expression pattern, clinical significance, and biological function in osteosarcoma (OS). In the present study, lncRNA HOTTIP expression in OS tissues was examined and its correlation with clinicopathological features and patient prognosis was analyzed. In vitro assays were performed to understand the biological roles of lncRNA HOTTIP in OS progression. In the study, we found that HOTTIP expression was up-regulated in OS tissues, and correlated with advanced clinical stage and distant metastasis. OS patients with high HOTTIP expression level had poorer overall survival than those with low HOTTIP expression. Multivariable Cox proportional hazards regression analysis suggested that increased HOTTIP expression was an independent prognostic factor of overall survival in OS patients. Moreover, the results of in vitro assays showed that the suppression of HOTTIP in OS cells significantly reduced cell proliferation, migration and invasion ability. Our study demonstrated that lncRNA HOTTIP play critical roles in OS progression and could represent a novel prognostic marker and potential therapeutic target in OS patients.

摘要

长链非编码RNA(lncRNAs)已被证明在癌症发生和发展中起关键作用。在本研究中,我们聚焦于lncRNA HOTTIP,并研究了其在骨肉瘤(OS)中的表达模式、临床意义及生物学功能。在本研究中,检测了OS组织中lncRNA HOTTIP的表达,并分析了其与临床病理特征及患者预后的相关性。进行了体外实验以了解lncRNA HOTTIP在OS进展中的生物学作用。在该研究中,我们发现HOTTIP在OS组织中表达上调,且与临床晚期和远处转移相关。HOTTIP表达水平高的OS患者总生存期比表达水平低的患者更差。多变量Cox比例风险回归分析表明,HOTTIP表达增加是OS患者总生存期的独立预后因素。此外,体外实验结果显示,抑制OS细胞中的HOTTIP可显著降低细胞增殖、迁移和侵袭能力。我们的研究表明,lncRNA HOTTIP在OS进展中起关键作用,可能是OS患者的一种新型预后标志物和潜在治疗靶点。

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本文引用的文献

1
The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer.长链非编码RNA HOTTIP通过调控HOXA13促进胰腺癌进展及吉西他滨耐药。
J Transl Med. 2015 Mar 12;13:84. doi: 10.1186/s12967-015-0442-z.
2
Overexpression of Long Non-Coding RNA HOTAIR Promotes Tumor Growth and Metastasis in Human Osteosarcoma.长链非编码RNA HOTAIR的过表达促进人骨肉瘤的肿瘤生长和转移。
Mol Cells. 2015 May;38(5):432-40. doi: 10.14348/molcells.2015.2327. Epub 2015 Feb 17.
3
Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b.长链非编码 RNA HOTTIP 在肝癌中常被上调,并且是肿瘤抑制 miR-125b 的靶标。
Liver Int. 2015 May;35(5):1597-606. doi: 10.1111/liv.12746. Epub 2015 Jan 27.
4
Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer.长链非编码RNA-LET是一种阳性预后因素,在胆囊癌中表现出肿瘤抑制活性。
Mol Carcinog. 2015 Nov;54(11):1397-406. doi: 10.1002/mc.22215. Epub 2014 Sep 11.
5
Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer.长链非编码RNA GAS5表达降低预示胃癌预后不良并促进其细胞增殖。
BMC Cancer. 2014 May 6;14:319. doi: 10.1186/1471-2407-14-319.
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Long non-coding RNAs: new players in cell differentiation and development.长非编码 RNA:细胞分化和发育中的新角色。
Nat Rev Genet. 2014 Jan;15(1):7-21. doi: 10.1038/nrg3606. Epub 2013 Dec 3.
7
Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients.长链非编码 RNA HOTTIP/HOXA13 的表达与疾病进展相关,并可预测肝癌患者的预后。
Hepatology. 2014 Mar;59(3):911-23. doi: 10.1002/hep.26740. Epub 2014 Jan 28.
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Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.长链非编码 RNA MALAT-1 是一种治疗去势抵抗性前列腺癌的新的潜在治疗靶点。
J Urol. 2013 Dec;190(6):2278-87. doi: 10.1016/j.juro.2013.07.001. Epub 2013 Jul 8.
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Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis.长链非编码RNA TUG1的下调抑制骨肉瘤细胞增殖并促进其凋亡。
Asian Pac J Cancer Prev. 2013;14(4):2311-5. doi: 10.7314/apjcp.2013.14.4.2311.
10
Molecular mechanisms of long noncoding RNAs.长非编码 RNA 的分子机制。
Mol Cell. 2011 Sep 16;43(6):904-14. doi: 10.1016/j.molcel.2011.08.018.