Mo Xing-Bo, Wu Long-Fei, Lu Xin, Zhu Xiao-Wei, Xia Wei, Wang Lan, He Pei, Bing Peng-Fei, Zhang Yong-Hong, Deng Fei-Yan, Lei Shu-Feng
Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, 215123, People's Republic of China.
Funct Integr Genomics. 2019 Mar;19(2):217-225. doi: 10.1007/s10142-018-0638-4. Epub 2018 Oct 2.
One major function of lncRNA is to regulate the expression of mRNA, but the patterns of their interactions were largely unknown. We attempted to construct lncRNA-mRNA interaction modules at a genome-wide scale. We performed a genome-wide lncRNA-mRNA eQTL analysis in peripheral blood mononuclear cells of 43 individuals, followed by weighted gene co-expression network analysis and functional enrichment analysis which sought to detect functional modules. There were 4627 significant cis lnc-eQTL pairs (P < 1.4 × 10) and 1,587,128 significant trans lnc-eQTL pairs (P < 3.46 × 10). We detected 11 eQTL modules for the lnc-eQTL networks. Among them, five modules showed significant enrichments in GO terms, and three modules showed significant enrichments in specific KEGG pathways (e.g., Toll-like receptor, PI3K-Akt, NF-kappa B, and TNF signaling pathways). lncRNA-protein interaction analysis showed that some well-known functional lncRNAs (HOTAIR, CCDC26, RHPN1-AS1, WT1-AS, and TCL6) in the eQTL module interacted with genes in focal adhesion and PI3K-Akt signaling pathway. We identified biologically functional lncRNA-mRNA interaction modules by integrating eQTL and weighted gene co-expression network analysis. Integrative analysis of lncRNA and mRNA data by applying eQTL analysis and weighted gene co-expression network analysis methods could be helpful for functional annotation of lncRNAs.
长链非编码RNA（lncRNA）的一个主要功能是调节信使核糖核酸（mRNA）的表达，但其相互作用模式在很大程度上尚不清楚。我们试图在全基因组范围内构建lncRNA-mRNA相互作用模块。我们对43名个体的外周血单个核细胞进行了全基因组lncRNA-mRNA表达数量性状基因座（eQTL）分析，随后进行加权基因共表达网络分析和功能富集分析以检测功能模块。有4627对显著的顺式lnc-eQTL对（P < 1.4×10）和1587128对显著的反式lnc-eQTL对（P < 3.46×10）。我们检测到lnc-eQTL网络的11个eQTL模块。其中，五个模块在基因本体（GO）术语中显示出显著富集，三个模块在特定的京都基因与基因组百科全书（KEGG）通路（如Toll样受体、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）、核因子κB（NF-κB）和肿瘤坏死因子（TNF）信号通路）中显示出显著富集。lncRNA-蛋白质相互作用分析表明，eQTL模块中的一些知名功能性lncRNA（HOTAIR、CCDC26、RHPN1-AS1、WT1-AS和TCL6）与粘着斑和PI3K-Akt信号通路中的基因相互作用。我们通过整合eQTL和加权基因共表达网络分析鉴定了具有生物学功能的lncRNA-mRNA相互作用模块。应用eQTL分析和加权基因共表达网络分析方法对lncRNA和mRNA数据进行综合分析可能有助于lncRNA的功能注释。
