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人膀胱尿路上皮癌中lncRNA表达谱的基因芯片分析

Gene microarray analysis of the lncRNA expression profile in human urothelial carcinoma of the bladder.

作者信息

Luo Huarong, Zhao Xin, Wan Xiaodong, Huang Shengsong, Wu Denglong

机构信息

Department of Urology, Tongji Hospital of Tongji University Shanghai 200065, China.

出版信息

Int J Clin Exp Med. 2014 May 15;7(5):1244-54. eCollection 2014.

Abstract

OBJECTIVE

To analyze the expression profile variation of lncRNAs in normal urinary bladder tissue and urothelial carcinoma of the urinary bladder through microarray technology. The differentially expressed lncRNAs were identified and classified, and their biological information was analyzed. The data obtained in the study will prove helpful for the diagnosis, treatment, and prevention of urothelial carcinoma of the bladder.

MATERIALS AND METHODS

Three specimens of urothelial carcinoma of the bladder and three specimens of normal bladder tissue were identified by histology. The total RNA was isolated from the bladder urothelial carcinomas and normal tissue and purified. The targets were mixed and hybridized with the genes on the microarray, which contained thirty thousand lncRNAs. The bladder urothelial carcinomas were then compared with the normal bladder tissue. The lncRNAs that were differentially expressed between the two groups were identified based on the signal-to-noise ratios using the Agilent Feature Extraction software and were analyzed with the Agilent Genespring GX software (Agilent). The outcome was obtained, and the biological information of these genes was deposited in GenBank.

RESULTS

The expression profile of lncRNAs was significantly different between normal bladder tissue and urothelial carcinoma of the bladder. Compared with normal bladder tissue, 1,122 lncRNAs exhibited at least a twofold, significant difference (P < 0.05) and are thus regarded as differentially expressed lncRNAs. Of these, 734 and 388 lncRNAs were upregulated and down regulated. The differentially expressed lncRNAs in the urothelial carcinoma of the bladder are distributed on every chromosome, and most of these lncRNAs are distributed on chromosomes 1, 2, 3, 4, 6, and X.

CONCLUSIONS

Urothelial carcinoma of the bladder is a complicated disease that involves the regulation of multiple genes and the participation of multiple chromosomes. Some of the differentially expressed lncRNAs that were upregulated, such as AK124776, lincRNA-RAB12-1, KRT8P25, RP11-474J18.4, AC000110.1, KRT8P13, KRT8P10, BC072678, and downregulated, such as nc-HOXB9-206, RP11-160A10.2, nc-HOXA11-86, nc-HOXD10-7, nc-HOXB9-205, CES4, nc-HOXD12-3, systematic research on these lncRNAs will help clarify the mechanisms of urothelial carcinoma of the bladder and guide the early diagnosis and treatment of this cancer in the future.

摘要

目的

通过微阵列技术分析lncRNAs在正常膀胱组织和膀胱尿路上皮癌中的表达谱变化。鉴定并分类差异表达的lncRNAs,并分析其生物学信息。本研究获得的数据将有助于膀胱尿路上皮癌的诊断、治疗和预防。

材料与方法

通过组织学鉴定3例膀胱尿路上皮癌标本和3例正常膀胱组织标本。从膀胱尿路上皮癌和正常组织中分离并纯化总RNA。将靶标与包含三万个lncRNAs的微阵列上的基因混合并杂交。然后将膀胱尿路上皮癌与正常膀胱组织进行比较。使用安捷伦特征提取软件基于信噪比鉴定两组之间差异表达的lncRNAs,并使用安捷伦基因弹簧GX软件(安捷伦)进行分析。获得结果,并将这些基因的生物学信息存入GenBank。

结果

正常膀胱组织和膀胱尿路上皮癌中lncRNAs的表达谱存在显著差异。与正常膀胱组织相比,1122个lncRNAs表现出至少两倍的显著差异(P < 0.05),因此被视为差异表达的lncRNAs。其中,734个lncRNAs上调,388个lncRNAs下调。膀胱尿路上皮癌中差异表达的lncRNAs分布在每条染色体上,其中大多数lncRNAs分布在1、2、3、4、6和X染色体上。

结论

膀胱尿路上皮癌是一种复杂的疾病,涉及多个基因的调控和多条染色体的参与。一些上调的差异表达lncRNAs,如AK124776、lincRNA-RAB12-1、KRT8P25、RP11-474J18.4、AC000110.1、KRT8P13、KRT8P10、BC072678,以及下调的lncRNAs,如nc-HOXB9-206、RP11-160A10.2、nc-HOXA11-86、nc-HOXD10-7、nc-HOXB9-205、CES4、nc-HOXD12-3,对这些lncRNAs进行系统研究将有助于阐明膀胱尿路上皮癌的发病机制,并在未来指导该癌症的早期诊断和治疗。

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