Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Sci Rep. 2017 Mar 24;7(1):395. doi: 10.1038/s41598-017-00327-0.
Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.
长链非编码 RNA（lncRNAs）的异常表达被认为是膀胱癌（BC）的一个关键组成部分，lncRNAs 与 BC 的发展和进展有关，尽管它们的总体表达和功能意义尚不清楚。我们的研究旨在确定在 BC 发生中具有功能作用的新型 lncRNA。RNA 测序用于鉴定 8 个正常和 72 个 BC 样本中异常表达的 lncRNAs。我们鉴定了 89 个在 BC 中明显失调的 lncRNAs。选择了 5 个 lncRNA；LINC00958、LINC01296、LINC00355、LNC-CMC1-1 和 LNC-ALX1-2 进行进一步分析。体外沉默 LINC00958 或 LINC01296 可降低细胞活力和迁移。LINC00958 的敲低也影响侵袭和抗凋亡。这些细胞效应可能与参与细胞死亡/存活、增殖和细胞运动的蛋白编码 mRNA 的直接/间接调节有关。最后，我们表明 LINC00958 结合参与翻译起始和 RNA 转录后修饰的蛋白质，包括 Metadherin，它先前与 BC 有关。我们的分析鉴定了 BC 中的新型 lncRNA，它们可能作为致癌驱动子发挥作用，通过与参与翻译起始和/或 RNA 转录后修饰的蛋白质相互作用，促进侵袭性癌表型。
