膀胱癌中lncRNAs和circRNAs差异表达谱及其相关共表达和ceRNA网络的综合分析
Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma.
作者信息
Huang Mengge, Zhong Zhenyu, Lv Mengxin, Shu Jing, Tian Qiang, Chen Junxia
机构信息
College of Clinical Medicine, Southwest Medical University, Luzhou 646000, China.
The First Clinical College, Chongqing Medical University, Chongqing 400016, China.
出版信息
Oncotarget. 2016 Jul 26;7(30):47186-47200. doi: 10.18632/oncotarget.9706.
Accumulating evidences indicate that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in tumorigenesis. However, the mechanisms remain largely unknown. To explore lncRNAs and circRNAs expression profiling and their biological functions in bladder cancer, we surveyed the lncRNA/circRNA and mRNA expression profiles of bladder cancer and para-cancer tissues using microarray for four patients. Thousands of significantly changed lncRNAs and mRNAs as well as hundreds of circRNAs were identified. Five dysregulated lncRNAs and four mRNAs were confirmed by quantitative real-time PCR in 30 pairs of samples. GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Further more, we constructed correlated expression networks including coding-noncoding co-expression (CNC), competing endogenous RNAs (ceRNA), cis regulation, lncRNAs-transcription factor (TF)-mRNA with bioinformatics methods. Co-expression analysis showed lncRNA APLP2 expression is correlated with apoptosis-related genes, including PTEN and TP53INP1. CeRNA network inferred that lncRNA H19 and circRNA MYLK could bind competitively with miRNA-29a-3p increasing target gene DNMT3B, VEGFA and ITGB1 expressions. Moreover, the nearby genes pattern displayed that overexpressing ADAM2 and C8orf4 are cis-regulated by lncRNA RP11-359E19.2, involving in progression of bladder cancer. In addition, lncRNAs-TF-mRNA diagram indicated that lncRNA BC041488 could trans-regulate CDK1 mRNA expression through SRF transcription factor. Taken together, these results suggested lncRNAs and circRNAs could implicate in the pathogenesis and development of bladder cancer. Our findings provide a novel perspective on lncRNAs and circRNAs and lay the foundation for future research of potential roles of lncRNAs and circRNAs in bladder carcinoma.
越来越多的证据表明,长链非编码RNA(lncRNAs)和环状RNA(circRNAs)在肿瘤发生过程中发挥着重要作用。然而,其机制仍 largely 未知。为了探索lncRNAs和circRNAs在膀胱癌中的表达谱及其生物学功能,我们使用微阵列技术对4例患者的膀胱癌组织和癌旁组织进行了lncRNA/circRNA和mRNA表达谱检测。鉴定出了数千个显著变化的lncRNAs和mRNAs以及数百个circRNAs。通过定量实时PCR在30对样本中验证了5个失调的lncRNAs和4个mRNAs。进行了GO和KEGG通路富集分析以确定显著失调基因的主要功能。此外,我们用生物信息学方法构建了包括编码-非编码共表达(CNC)、竞争性内源RNA(ceRNA)、顺式调控、lncRNAs-转录因子(TF)-mRNA的相关表达网络。共表达分析显示lncRNA APLP2的表达与凋亡相关基因(包括PTEN和TP53INP1)相关。ceRNA网络推断lncRNA H19和circRNA MYLK可以与miRNA-29a-3p竞争性结合,增加靶基因DNMT3B、VEGFA和ITGB1的表达。此外,附近基因模式显示lncRNA RP11-359E19.2对过表达的ADAM2和C8orf4进行顺式调控,参与膀胱癌的进展。另外,lncRNAs-TF-mRNA图谱表明lncRNA BC041488可以通过SRF转录因子反式调控CDK1 mRNA的表达。综上所述,这些结果表明lncRNAs和circRNAs可能参与膀胱癌的发病机制和发展。我们的发现为lncRNAs和circRNAs提供了一个新的视角,并为未来研究lncRNAs和circRNAs在膀胱癌中的潜在作用奠定了基础。