Dong Rui, Jia Deshui, Xue Ping, Cui Ximao, Li Kai, Zheng Shan, He Xianghuo, Dong Kuiran
Department of Pediatric Surgery, Children's Hospital of Fudan University and The Key Laboratory of Neonatal Disease, Chinese Ministry of Health, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2014 Jan 17;9(1):e85599. doi: 10.1371/journal.pone.0085599. eCollection 2014.
Long noncoding RNAs (lncRNAs) have crucial roles in cancer biology. We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma. Hepatoblastoma and normal liver tissue samples were obtained from hepatoblastoma patients. The genome-wide analysis of lncRNA expression in these tissues was performed using a 4×180 K lncRNA microarray and Sureprint G3 Human lncRNA Chips. Quantitative RT-PCR (qRT-PCR) was performed to confirm these results. The differential expressions of lncRNAs and mRNAs were identified through fold-change filtering. Gene Ontology (GO) and pathway analyses were performed using the standard enrichment computation method. Associations between lncRNAs and adjacent protein-coding genes were determined through complex transcriptional loci analysis. We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues. Among these, 1757 lncRNAs were upregulated more than two-fold relative to normal tissues and 979 lncRNAs were downregulated. Moreover, in hepatoblastoma there were 420 matched lncRNA-mRNA pairs for 120 differentially expressed lncRNAs, and 167 differentially expressed mRNAs. The co-expression network analysis predicted 252 network nodes and 420 connections between 120 lncRNAs and 132 coding genes. Within this co-expression network, 369 pairs were positive, and 51 pairs were negative. Lastly, qRT-PCR data verified six upregulated and downregulated lncRNAs in hepatoblastoma, plus endothelial cell-specific molecule 1 (ESM1) mRNA. Our results demonstrated that expression of these aberrant lncRNAs could respond to hepatoblastoma development. Further study of these lncRNAs could provide useful insight into hepatoblastoma biology.
长链非编码RNA（lncRNAs）在癌症生物学中发挥着关键作用。我们对肝母细胞瘤组织中的lncRNA表达进行了全基因组分析，以确定用于肝母细胞瘤进一步研究的新靶点。肝母细胞瘤和正常肝组织样本取自肝母细胞瘤患者。使用4×180K lncRNA微阵列和Sureprint G3人类lncRNA芯片对这些组织中的lncRNA表达进行全基因组分析。进行定量逆转录聚合酶链反应（qRT-PCR）以证实这些结果。通过倍数变化筛选来鉴定lncRNAs和mRNAs的差异表达。使用标准富集计算方法进行基因本体论（GO）和通路分析。通过复杂转录位点分析确定lncRNAs与相邻蛋白质编码基因之间的关联。我们发现2736个lncRNAs在肝母细胞瘤组织中差异表达。其中，相对于正常组织，1757个lncRNAs上调超过两倍，979个lncRNAs下调。此外，在肝母细胞瘤中，1
