Identification of novel long non-coding RNAs in clear cell renal cell carcinoma.

Identification of novel long non-coding RNAs in clear cell renal cell carcinoma.
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DOI:
10.1186/s13148-015-0047-7
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发表时间:
2015
影响因子:
5.7
通讯作者:
Ellinger J
Ellinger J
中科院分区:
医学1区
文献类型:
--
作者:
Blondeau JJ;Deng M;Syring I;Schrödter S;Schmidt D;Perner S;Müller SC;Ellinger J

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长链非编码RNA(lncRNA)在肾癌的发生发展中起重要作用,但对lncRNA在肾癌中的表达了解甚少。作为生物标志物开发的基础,我们旨在探索透明细胞肾细胞癌(ccRCC)组织中的lncRNA表达谱。采用基因芯片技术检测15例正常肾组织和恶性肾组织中17,512个lncRNA中32,183个lncRNA转录本的表达。在55例ccRCC和52例正常肾标本中使用定量实时PCR进行验证。进行计算分析以确定lncRNA-microRNA(MiRTarget 2)和lncRNA-蛋白质(catRAPID omics)相互作用。我们在ccRCC组织中鉴定了1,308个失调的转录物(表达变化>2倍;上调:568,下调:740)。其中,使用PCR验证异常表达:lnc-BMP 2 -2(平均表达变化:在ccRCC中,lnc-CPN 2 -1(13倍)、lnc-FZD 1 -2(9倍)、lnc-ITPR 2 -3(15倍)、lnc-SLC 30 A4 -1(15倍)和lnc-SPAM 1 -6(10倍)高度过表达,而lnc-ACACA-1(10倍)在ccRCC中高度过表达。LNC-F0 XG 1 -2(19倍)、LNC-LCP 2 -2(2倍)、LNC-RP 3 - 368 B 9(19倍)和LNC-TTC 34 -3(314倍)下调。lncRNA表达与临床病理参数无相关性。计算分析显示,这些lncRNA参与RNA-蛋白质网络,涉及RNA的剪接、结合、转运、定位和加工。小干扰RNA(siRNA)介导的lnc-BMP 2 -2和lnc-CPN 2 -1的敲低不影响细胞增殖。我们鉴定了许多新的在ccRCC中失调的lncRNA转录物,其可用于新的诊断生物标志物。本文的在线版本(doi:10.1186/s13148-015-0047-7)包含补充材料,可供授权用户使用。
Long non-coding RNAs (lncRNA) play an important role in carcinogenesis; knowledge on lncRNA expression in renal cell carcinoma is rudimental. As a basis for biomarker development, we aimed to explore the lncRNA expression profile in clear cell renal cell carcinoma (ccRCC) tissue. Microarray experiments were performed to determine the expression of 32,183 lncRNA transcripts belonging to 17,512 lncRNAs in 15 corresponding normal and malignant renal tissues. Validation was performed using quantitative real-time PCR in 55 ccRCC and 52 normal renal specimens. Computational analysis was performed to determine lncRNA-microRNA (MiRTarget2) and lncRNA-protein (catRAPID omics) interactions. We identified 1,308 dysregulated transcripts (expression change >2-fold; upregulated: 568, downregulated: 740) in ccRCC tissue. Among these, aberrant expression was validated using PCR: lnc-BMP2-2 (mean expression change: 37-fold), lnc-CPN2-1 (13-fold), lnc-FZD1-2 (9-fold), lnc-ITPR2-3 (15-fold), lnc-SLC30A4-1 (15-fold), and lnc-SPAM1-6 (10-fold) were highly overexpressed in ccRCC, whereas lnc-ACACA-1 (135-fold), lnc-FOXG1-2 (19-fold), lnc-LCP2-2 (2-fold), lnc-RP3-368B9 (19-fold), and lnc-TTC34-3 (314-fold) were downregulated. There was no correlation between lncRNA expression with clinical-pathological parameters. Computational analyses revealed that these lncRNAs are involved in RNA-protein networks related to splicing, binding, transport, localization, and processing of RNA. Small interfering RNA (siRNA)-mediated knockdown of lnc-BMP2-2 and lnc-CPN2-1 did not influence cell proliferation. We identified many novel lncRNA transcripts dysregulated in ccRCC which may be useful for novel diagnostic biomarkers. The online version of this article (doi:10.1186/s13148-015-0047-7) contains supplementary material, which is available to authorized users.
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期刊: Bioinformatics (Oxford, England)
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作者:
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期刊: NATURE GENETICS
影响因子: 30.8
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DOI: 10.1093/nar/gks915
发表时间: 2013-01
影响因子: 14.9
作者:
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