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膀胱癌细胞中与UCA1相关的微小RNA的基因表达谱分析。

Gene expression profiling of microRNAs associated with UCA1 in bladder cancer cells.

作者信息

Xie Xiaojuan, Pan Jingjing, Wei Liqiang, Wu Shouzhen, Hou Huilian, Li Xu, Chen Wei

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Shaanxi Center for Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.

出版信息

Int J Oncol. 2016 Apr;48(4):1617-27. doi: 10.3892/ijo.2016.3357. Epub 2016 Jan 25.

Abstract

Emerging evidence indicates that non-coding RNAs, such as lncRNAs and microRNAs, play important roles in diverse diseases, such as cancer, immune diseases and cardiovascular diseases. Interestingly, lncRNAs could directly or indirectly regulate the expression of miRNAs. However, the expression profiling of miRNAs associated with UCA1 in bladder cancer remains unknown. Here, we used Illumina deep sequencing to sequence miRNA libraries from both the UCA1 knockdown and normal high-expression 5637 cells. We identified 225 and 235 miRNAs expressed in 5637 cells of normal high-expression and knockdown of UCA1, respectively. Overall, expression of 75 miRNAs showed significant difference associated with UCA1, of which 38 were upregulated and 37 downregulated with UCA1 knockdown. GO analysis of the host target genes revealed that these aberrantly regulated miRNAs were involved in complex cellular pathways, including biological process, cellular component and molecular function. We selected 8 candidate miRNAs associated with UCA1 and predicted their targeted mRNAs, and found that p27kip1 was a crucial downstream molecule for these 8 miRNAs, especially for miR-196a. KEGG pathway analysis showed that PI3K-Akt signaling pathway was involved in regulating these 8 candidant miRNAs. Among these 8 candidant miRNAs, we observed the correlation among UCA1, miR-196a and the host target mRNA, p27kip1, in bladder cancer cells and tissues. UCA1 was upregulated by miR-196a and positively correlated with miR-196a, whereas UCA1 and miR-196a were negatively correlated with p27kip1, which was downregulated in bladder cancer patients. Thus, our findings provided valuable information on miRNAs associated with UCA1 in bladder cancer, which could be helpful to further explore the related genes and molecular networks fundamental in bladder cancer progression.

摘要

新出现的证据表明,长链非编码RNA(lncRNAs)和微小RNA(microRNAs)等非编码RNA在多种疾病中发挥重要作用,如癌症、免疫疾病和心血管疾病。有趣的是,lncRNAs可直接或间接调节miRNAs的表达。然而,膀胱癌中与UCA1相关的miRNAs的表达谱仍不清楚。在此,我们使用Illumina深度测序对UCA1敲低和正常高表达的5637细胞的miRNA文库进行测序。我们分别在正常高表达和UCA1敲低的5637细胞中鉴定出225个和235个表达的miRNAs。总体而言,75个miRNAs的表达与UCA1存在显著差异,其中38个在UCA1敲低时上调,37个下调。对宿主靶基因的基因本体(GO)分析表明,这些异常调节的miRNAs参与复杂的细胞途径,包括生物学过程、细胞成分和分子功能。我们选择了8个与UCA1相关的候选miRNAs并预测了它们的靶mRNA,发现p27kip1是这8个miRNAs的关键下游分子,尤其是对于miR-196a。京都基因与基因组百科全书(KEGG)通路分析表明,PI3K-Akt信号通路参与调节这8个候选miRNAs。在这8个候选miRNAs中,我们观察到膀胱癌细胞和组织中UCA1、miR-196a及其宿主靶mRNA p27kip1之间的相关性。UCA1被miR-196a上调且与miR-196a呈正相关,而UCA1和miR-196a与p27kip1呈负相关,p27kip1在膀胱癌患者中下调。因此,我们的研究结果提供了关于膀胱癌中与UCA1相关的miRNAs的有价值信息,这可能有助于进一步探索膀胱癌进展中相关的基因和分子网络。

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