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长链非编码RNA MALAT1的上调与透明细胞肾细胞癌的肿瘤进展及不良预后相关。

Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma.

作者信息

Zhang Hai-min, Yang Feng-qiang, Chen Shao-Jun, Che Jianping, Zheng Jun-hua

机构信息

Department of Urology, Shanghai Tenth People's Hospital, Tongji University, No 301, Yanchang Mid-Road, Shanghai, 200072, China.

出版信息

Tumour Biol. 2015 Apr;36(4):2947-55. doi: 10.1007/s13277-014-2925-6. Epub 2014 Dec 6.

DOI:10.1007/s13277-014-2925-6
PMID:25480417
Abstract

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

摘要

长链非编码RNA(lncRNAs)已被作为一类新型的细胞过程调节因子进行研究,如细胞生长、凋亡和致癌作用。长链非编码RNA转移相关肺腺癌转录本1(MALAT1)最近被发现参与了多种癌症的肿瘤发生过程,如肺癌、胰腺癌和宫颈癌。然而,lncRNA MALAT1在透明细胞肾细胞癌(ccRCC)中的作用仍不清楚。通过定量实时PCR(qRT-PCR)评估lncRNA MALAT1在ccRCC组织和肾癌细胞系中的表达水平,并通过统计分析分析其与患者总生存期的关系。使用小干扰RNA(siRNA)抑制肾癌细胞中MALAT1的表达。进行体外实验以进一步探索其在肿瘤进展中的作用。与相邻的非肿瘤组织和正常人近端肾小管上皮细胞HK-2相比,MALAT1在ccRCC组织和肾癌细胞中的表达水平更高。MALAT1表达较高的ccRCC患者比MALAT1表达较低的患者具有更晚期的临床特征和更短的总生存时间。多因素分析表明,MALAT1表达状态是ccRCC患者总生存期的独立预测因子。此外,我们的数据表明,敲低MALAT1的表达可降低肾癌细胞的增殖、迁移和侵袭。我们的数据表明,lncRNA MALAT1是一种参与ccRCC进展的新型分子,这为潜在的预后生物标志物和治疗靶点提供了依据。

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本文引用的文献

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The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1.
长链非编码 RNA(lncRNA)-MALAT-1 在肾细胞癌发病机制中的作用。
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Exploring Novel Genome Instability-associated lncRNAs and their Potential Function in Pan-Renal Cell Carcinoma.探索新型与基因组不稳定性相关的 lncRNAs 及其在肾细胞癌中的潜在功能。
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Prognostic significance of MALAT1 in clear cell renal cell carcinoma based on TCGA and GEO.基于 TCGA 和 GEO 数据库的 MALAT1 在肾透明细胞癌中的预后意义。
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