Chang Lei, Qi Haolong, Xiao Yusha, Li Changsheng, Wang Yitao, Guo Tao, Liu Zhisu, Liu Quanyan
Department of General Surgery, Zhongnan Hospital, Wuhan University, Donghu Road 169, Wuhan 430071, PR China.
Department of General Surgery, Zhongnan Hospital, Wuhan University, Donghu Road 169, Wuhan 430071, PR China.
Growth Horm IGF Res. 2016 Aug;29:11-20. doi: 10.1016/j.ghir.2016.03.003. Epub 2016 Apr 3.
Accumulating evidence has indicated that noncoding RNAs (ncRNAs) have important regulatory potential in various biological processes. The molecular mechanisms by which growth hormone receptor (GHR) deficiency protects against age-related pathologies, reduces the incidence and delays the occurrence of fatal neoplasms are unclear. The aim of this study was to investigate miRNA, lncRNA and mRNA expression profiles and the potential functional roles of these RNA molecules in GHR knockout (GHR-KO) mice. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in wild type control mice and in GHR-KO mice. Differential expression, pathway and gene network analyses were developed to identify the possible biological roles of functional RNA molecules. Compared to wild type control mice, 1695 lncRNAs, 914 mRNAs and 9 miRNAs were upregulated and 1747 lncRNAs, 786 mRNAs and 21 miRNAs were downregulated in female GHR-KO mice. Moreover, 1265 lncRNAs, 724 mRNAs and 41 miRNAs were upregulated and 1377 lncRNAs, 765 mRNAs and 16 miRNAs were downregulated in male GHR-KO mice compared to wild type mice. Co-expression analysis of mRNAs, lncRNAs, and miRNAs showed that mRNAs including Hemxi2, Ero1Ib, 4933434i20RIK, Pde7a and Lgals1, lncRNAs including ASMM9PARTA014848, EL605414-P1, ASMM9PARTA051724, ASMM9PARTA045378 and ASMM9PARTA049185, and miRNAs including miR-188-3p, miR-690, miR-709 and miR-710 are situated at the core position of a three-dimensional lncRNA-mRNA-miRNA regulatory network. KEGG analysis showed that the most significantly regulated pathway was steroid hormone biosynthesis. We identified a set of lncRNAs, miRNAs and mRNAs that were aberrantly expressed in GHR-KO mice. Our results provide a foundation and an expansive view of the biological activities of the GHR.
越来越多的证据表明，非编码RNA（ncRNAs）在各种生物学过程中具有重要的调控潜力。生长激素受体（GHR）缺乏症预防与年龄相关的疾病、降低致命性肿瘤的发病率并延迟其发生的分子机制尚不清楚。本研究的目的是调查微小RNA（miRNA）、长链非编码RNA（lncRNA）和信使RNA（mRNA）的表达谱，以及这些RNA分子在GHR基因敲除（GHR-KO）小鼠中的潜在功能作用。测定野生型对照小鼠和GHR-KO小鼠中miRNA、lncRNA和mRNA的微阵列表达谱。开展差异表达、通路和基因网络分析，以确定功能性RNA分子可能的生物学作用。与野生型对照小鼠相比，雌性GHR-KO小鼠中有1695个lncRNA、914个mRNA和9个miRNA上调，1747个lncRNA、786个mRNA和21个miRNA下调。此外，与野生型小鼠相比，雄性GHR-KO小鼠中有1265个lncRNA、724个mRNA和41个miRNA上调，1377个lncRNA、765个mRNA和16个miRNA下调。mRNA、lncRNA和miRNA的共表达分析表明，包括Hemxi2、Ero1Ib、4933434i20RIK、Pde7a和Lgals1在内的mRNA，包括ASMM9PARTA014848、EL605414-P1、ASMM9PARTA051724、ASMM9PARTA045378和ASMM9PARTA049185在内的lncRNA，以及包括miR-188-3p、miR-690、miR-709和miR-710在内的miRNA位于三维lncRNA-mRNA-miRNA调控网络的核心位置。京都基因与基因组百科全书（KEGG）分析表明，调控最显著的通路是类固醇激素生物合成。我们鉴定出一组在GHR-KO小鼠中异常表达的lncRNA、miRNA和mRNA。我们的结果为GHR的生物学活性提供了基础和广阔的视野。
