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

被引:78
作者
Blondeau, Jasmine J. C. [1 ]
Deng, Mario [2 ,3 ,4 ]
Syring, Isabella [1 ,3 ]
Schroedter, Sarah [1 ]
Schmidt, Doris [1 ]
Perner, Sven [2 ,3 ,4 ]
Mueller, Stefan C. [1 ]
Ellinger, Joerg [1 ]
机构
[1] Univ Hosp Bonn, Dept Urol, Bonn, Germany
[2] Univ Hosp Bonn, Inst Pathol, Bonn, Germany
[3] Univ Hosp Bonn, Dept Prostate Canc Res, Bonn, Germany
[4] Univ Hosp Bonn, Ctr Integrated Oncol, Bonn, Germany
关键词
PROSTATE-CANCER; PREDICTION; PLASMA; EXPRESSION; BIOMARKER; SERVER; HULC;
D O I
10.1186/s13148-015-0047-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: 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. Results: 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. Conclusions: We identified many novel lncRNA transcripts dysregulated in ccRCC which may be useful for novel diagnostic biomarkers.
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页数:10
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