Department of Urology, University Hospital Bonn, Bonn, Germany.
Institute of Pathology, University Hospital Bonn, Bonn, Germany ; Department of Prostate Cancer Research, University Hospital Bonn, Bonn, Germany ; Center of Integrated Oncology, University Hospital Bonn, Bonn, Germany.
Clin Epigenetics. 2015 Feb 8;7(1):10. doi: 10.1186/s13148-015-0047-7. eCollection 2015.
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.
长非编码 RNA（lncRNA）在肿瘤发生中发挥重要作用；有关肾透明细胞癌（ccRCC）中 lncRNA 表达的知识还很初步。作为生物标志物开发的基础，我们旨在探索 ccRCC 组织中的 lncRNA 表达谱。
进行了微阵列实验，以确定 15 对相应的正常和恶性肾组织中属于 17512 个 lncRNA 的 32183 个 lncRNA 转录本的表达。在 55 个 ccRCC 和 52 个正常肾标本中使用定量实时 PCR 进行验证。进行了计算分析以确定 lncRNA- microRNA（MiRTarget2）和 lncRNA-蛋白质（catRAPID omics）相互作用。我们在 ccRCC 组织中鉴定出 1308 个失调转录本（表达变化> 2 倍；上调：568，下调：740）。其中，使用 PCR 验证了异常表达：lnc-BMP2-2（平均表达变化：37 倍），lnc-CPN2-1（13 倍），lnc-FZD1-2（9 倍），lnc-ITPR2-3（15 倍），lnc-SLC30A4-1（15 倍）和 lnc-SPAM1-6（10 倍）在 ccRCC 中高度过表达，而 lnc-ACACA-1（135 倍），lnc-FOXG1-2（19 倍），lnc-LCP2-2（2 倍），lnc-RP3-368B9（19 倍）和 lnc-TTC34-3（314 倍）下调。lncRNA 表达与临床病理参数之间没有相关性。计算分析表明，这些 lncRNA 参与了与剪接，结合，运输，定位和 RNA 加工有关的 RNA-蛋白质网络。siRNA 介导的 lnc-BMP2-2 和 lnc-CPN2-1 的敲低并不影响细胞增殖。
我们鉴定出许多在 ccRCC 中失调的新型 lncRNA 转录本，它们可能对新型诊断生物标志物有用。
