Interaction network of coexpressed mRNA, miRNA, and lncRNA activated by TGF‑β1 regulates EMT in human pulmonary epithelial cell.

Interaction network of coexpressed mRNA, miRNA, and lncRNA activated by TGF‑β1 regulates EMT in human pulmonary epithelial cell.
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TGF-β1激活的共表达mRNA、miRNA和lncRNA的相互作用网络调节人肺上皮细胞的EMT

DOI:
10.3892/mmr.2017.7653
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发表时间:
2017-12
影响因子:
3.4
通讯作者:
Lv C
Lv C
中科院分区:
医学4区
文献类型:
--
作者:
Liu H;Zhao X;Xiang J;Zhang J;Meng C;Zhang J;Li M;Song X;Lv C

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非编码RNA(ncRNA),如microRNA(miRNAs)和长链非编码RNA(lncRNA),在疾病发展的病理过程中发挥着越来越重要的作用。然而,mRNAs是否与miRNAs和lncRNAs相互作用以形成疾病中相互作用的调控网络仍然未知。本研究系统分析了人肺泡上皮细胞在TGF-β1激活的上皮-间质转化(EMT)过程中共表达的mRNA、miRNA和lncRNA的相互作用。对于EMT调节,共表达了24种mRNA、11种miRNA和33种lncRNA,并且彼此相互作用。进一步分析了共表达的mRNA、miRNA和lncRNA之间的相互作用,结果表明它们之间缺乏竞争性内源RNA(ceRNA)。这种相互调节可能与组蛋白修饰和转录因子募集等其他方式有关。然而,不能忽视ceRNA存在的可能性,因为lncRNA的丰度通常较低,蛋白质-RNA相互作用频繁混杂。因此,结论需要进一步的实验验证和确认。在这种情况下,破坏许多改变的疾病通路仍然是获得有效的基于通路的治疗的挑战之一。原因是一种特定的mRNA,miRNA或lncRNA可能靶向可能与疾病有关的多个基因。尽管如此,本研究的结果提供了基本的机制信息,可能的生物标志物和疾病,特别是肺肿瘤和纤维化的新的治疗策略。
Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play increasingly important roles in pathological processes involved in disease development. However, whether mRNAs interact with miRNAs and lncRNAs to form an interacting regulatory network in diseases remains unknown. In this study, the interaction of coexpressed mRNAs, miRNAs and lncRNAs during tumor growth factor-β1-activated (TGF-β1) epithelial-mesenchymal transition (EMT) was systematically analyzed in human alveolar epithelial cells. For EMT regulation, 24 mRNAs, 11 miRNAs and 33 lncRNAs were coexpressed, and interacted with one another. The interaction among coexpressed mRNAs, miRNAs and lncRNAs were further analyzed, and the results showed the lack of competing endogenous RNAs (ceRNAs) among them. The mutual regulation may be correlated with other modes, such as histone modification and transcription factor recruitment. However, the possibility of ceRNA existence cannot be ignored because of the generally low abundance of lncRNAs and frequent promiscuity of protein-RNA interactions. Thus, conclusions need further experimental identification and validation. In this context, disrupting many altered disease pathways remains one of the challenges in obtaining effective pathway-based therapy. The reason being that one specific mRNA, miRNA or lncRNA may target multiple genes that are potentially implicated in a disease. Nevertheless, the results of the present study provide basic mechanistic information, possible biomarkers and novel treatment strategies for diseases, particularly pulmonary tumor and fibrosis.
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