Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150006, P.R. China.
Department of Endocrinology, The Second Hospital of Harbin, Harbin, Heilongjiang 150006, P.R. China.
Int J Mol Med. 2019 Feb;43(2):927-935. doi: 10.3892/ijmm.2018.4026. Epub 2018 Dec 12.
Gestational diabetes mellitus (GDM) is a common disease affecting pregnant women. Recent studies have suggested that competing endogenous RNAs (ceRNAs), which compete with long non‑coding RNAs (lncRNAs) for microRNA (miRNA or miR) binding and indirectly regulate miRNA targets through competing interactions, play a critical role in disease. In this study, we present a computationally integrated approach with which to construct a lncRNA‑mediated ceRNA network (LCEN) in GDM by integrating RNA interactions and expression data. lncRNAs exhibited specific features and played critical roles in GDM‑associated LCEN. The construction of a global functional score profile revealed that ceRNAs had a high activity in GDM. We extracted several ceRNA modules and demonstrated that these modules had increased close interactions. We further discovered that these ceRNA modules may be utilized as specific and effective circulating biomarkers for GDM. Finally, functional analyses demonstrated that the GDM‑associated ceRNAs participated in the regulation of irisin and the thyroid hormone signaling pathway. It was suggested that there were close associations between the thyroid hormone and GDM. Collectively, ceRNAs may accelerate biomarker discovery and therapeutic development in GDM.
妊娠期糖尿病(GDM)是一种常见的妊娠妇女疾病。最近的研究表明,竞争内源性 RNA(ceRNA)通过竞争相互作用与长链非编码 RNA(lncRNA)竞争 miRNA(miRNA 或 miR)结合,并间接调节 miRNA 靶标,在疾病中发挥关键作用。在本研究中,我们提出了一种计算整合方法,通过整合 RNA 相互作用和表达数据,构建 GDM 中 lncRNA 介导的 ceRNA 网络(LCEN)。lncRNAs 表现出特定的特征,并在 GDM 相关的 LCEN 中发挥关键作用。构建全局功能评分谱表明 ceRNAs 在 GDM 中具有高活性。我们提取了几个 ceRNA 模块,并证明这些模块具有增加的紧密相互作用。我们进一步发现,这些 ceRNA 模块可用作 GDM 的特定和有效循环生物标志物。最后,功能分析表明,与 GDM 相关的 ceRNAs 参与了鸢尾素和甲状腺激素信号通路的调节。提示甲状腺激素与 GDM 之间存在密切关联。总之,ceRNA 可能加速 GDM 中的生物标志物发现和治疗开发。