Chen Xiaohua, Liu Binjian, Yang Rui, Guo Yong, Li Feng, Wang Lin, Hu Hanyang
School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Department of Laboratory Medicine, No.161 Hospital of PLA, Wuhan, China.
Oncotarget. 2016 Apr 26;7(17):23897-908. doi: 10.18632/oncotarget.8192.
Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in tumors. However, the genome-wide expression and roles of lncRNAs in colorectal cancer (CRC) remain unknown. Here, we systematically examined the global gene expressions in primary and synchronous liver metastases CRC tissue, in which thousands of aberrantly expressed lncRNAs were characterized. Co-expression analysis revealed that some lncRNAs correlated to their neighboring mRNAs in expression levels, whereas others formed networks with protein-coding genes in trans. We observed H3K4me3 was enriched at expressed lncRNA transcription start sites (TSSs) and correlated to dysregulated lncRNAs. Furthermore, we identified primary and metastasis tumor linked lncRNA signatures positively correlated with poor-prognosis gene set. Finally, functional experiments demonstrated two candidate lncRNAs were required for proliferation and migration of CRC cells. In summary, we provided a new framework for lncRNA associated clinical prognosis evaluation and target selection of gene therapy in CRC.
越来越多的证据凸显了长链非编码RNA（lncRNA）在肿瘤中的作用。然而，lncRNA在结直肠癌（CRC）中的全基因组表达及作用仍不清楚。在此，我们系统地检测了原发性和同步性肝转移CRC组织中的整体基因表达，鉴定出数千个异常表达的lncRNA。共表达分析显示，一些lncRNA在表达水平上与其邻近的mRNA相关，而其他lncRNA则与蛋白质编码基因形成反式网络。我们观察到H3K4me3在表达的lncRNA转录起始位点（TSS）富集，并与失调的lncRNA相关。此外，我们鉴定出与预后不良基因集呈正相关的原发性和转移性肿瘤相关lncRNA特征。最后，功能实验表明，两种候选lncRNA是CRC细胞增殖和迁移所必需的。总之，我们为CRC中lncRNA相关的临床预后评估和基因治疗靶点选择提供了一个新的框架。
