Wang Bin, Tang Dongyang, Zhang Ziyang, Wang Zhiwei
School of Life Science And Technology, Henan Institute of Science and Technology, Xinxiang, China.
Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, China.
J Cell Biochem. 2020 Feb;121(2):1491-1503. doi: 10.1002/jcb.29384. Epub 2019 Sep 9.
Emerging evidence has indicated that long noncoding RNA (lncRNA) plays crucial roles in regulating hepatocellular carcinoma (HCC) progression. However, a comprehensive lncRNA-transcription factor (TF)-message RNA (mRNA) in HCC remains absent. The aim of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in HCC. GSE124535 dataset was downloaded from the Gene Expression Omnibus database. Limma package in R was conducted to analyze abnormally expressed lncRNAs (differentially expressed lncRNAs [DELs]) and mRNAs (differentially expressed genes). The prognostic roles of screened DELs in HCC were evaluated at GEPIA. The expression of DELs that correlated with overall survival of HCC patients was further validated using circlncRNAnet, GEPIA, and StarBase. LncRNA-TF-mRNA potential triplets in HCC were predicted by LncMAP. After that, lncRNA-TF-mRNA networks were established using Cytoscape. A total of 20 upregulated and 17 downregulated DELs were identified in HCC tissues compared with adjacent noncancerous tissues. Six out of 20 upregulated and 6 out of 17 downregulated DELs were identified have significant impact on the overall survival of HCC patients. Results in circlncRNAnet, GEPIA, and Starbase confirmed the expression level of DELs obtained from GSE124535. Finally, the LncRNA-TF-mRNA regulatory networks for upregulated and downregulated lncRNA were established based on these analyses results. Among these lncRNAs in the network, the aberrantly expression of lncRNAs including LINC00511, RP11-290F5.1, MIR4435-2HG, and CTC-537E7.3 in HCC was first time reported to date. In the study, potential LncRNA-TF-mRNA regulatory networks were identified, which will advance our understanding concerning the progression of HCC.
新出现的证据表明,长链非编码RNA(lncRNA)在调节肝细胞癌(HCC)进展中起关键作用。然而,HCC中全面的lncRNA-转录因子(TF)-信使RNA(mRNA)研究仍未开展。本研究旨在识别HCC中异常表达的lncRNA以及相关的TF-mRNA网络。从基因表达综合数据库下载GSE124535数据集。使用R语言中的Limma软件包分析异常表达的lncRNA(差异表达lncRNA [DEL])和mRNA(差异表达基因)。在GEPIA中评估筛选出的DEL在HCC中的预后作用。使用circlncRNAnet、GEPIA和StarBase进一步验证与HCC患者总生存期相关的DEL的表达。通过LncMAP预测HCC中lncRNA-TF-mRNA潜在三联体。之后,使用Cytoscape建立lncRNA-TF-mRNA网络。与相邻非癌组织相比,在HCC组织中共鉴定出20个上调和17个下调的DEL。20个上调的DEL中有6个和17个下调的DEL中有6个被鉴定出对HCC患者的总生存期有显著影响。circlncRNAnet、GEPIA和Starbase的结果证实了从GSE124535获得的DEL的表达水平。最后,基于这些分析结果建立了上调和下调lncRNA的LncRNA-TF-mRNA调控网络。在该网络中的这些lncRNA中,包括LINC00511、RP11-290F5.1、MIR4435-2HG和CTC-537E7.3在内的lncRNA在HCC中的异常表达在本研究中首次被报道。在本研究中,识别出了潜在的LncRNA-TF-mRNA调控网络,这将增进我们对HCC进展的理解。