背景:先前的研究已经证明microRNA-147(miR-147)在炎症中的重要作用,辐射诱导的损伤,癌症,和一系列其他疾病。小鼠肺表现出高水平的miRNA,mRNA和lncRNA表达。然而,迄今为止,很少有研究集中在与miR-147相关的lncRNA-miRNA-mRNA竞争性内源性RNA(ceRNA)网络上,而在这种情况下lncRNA和miRNA的调控仍知之甚少.方法:建立miR-147-/-模型小鼠,收集肺组织样本进行RNA测序,和差异表达的lncRNAs,miRNA,并鉴定了mRNA。首先将这些lncRNAs的miRNA靶标和鉴定的miRNA重叠以促进靶标mRNA的预测,然后分析这些靶标和差异表达的mRNA之间的重叠。然后,对这些靶mRNA进行途径富集分析.这些结果最终用于建立miR-147相关的ceRNA网络。结果:相对于野生型小鼠,miR-147-/-小鼠的肺表现出91、43和71个显著上调的lncRNAs,miRNA,和mRNA,分别,以及114、31和156被显著下调。基于这些结果建立的lncRNA-miRNA-mRNA网络导致将Kcnh6鉴定为差异表达的hub基因候选物,并能够鉴定一系列调控关系。KEGG通路富集显示小鼠差异表达的lncRNAs和miRNAs的mRNA靶与肿瘤相关信号相关,子宫内膜癌,膀胱癌,和ErbB信号。结论:这些结果表明,miR-147-/-小鼠中鉴定的ceRNA网络塑造了肿瘤相关的信号传导活性,miR-147可能通过Kcnh6调节各种lncRNAs和miRNAs,最终影响肿瘤发生。lncRNA的未来研究,miRNA,在本研究中显示与miR-147相关的mRNA调控靶标可能最终导致鉴定新的临床相关靶标,通过这些靶标miR-147塑造癌症和其他疾病的发病机理。
Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.