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TGF-β1 激活的共表达 mRNA、miRNA 和 lncRNA 的相互作用网络调控人肺上皮细胞 EMT。

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

机构信息

Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, P.R. China.

Department of Clinical Nursing, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, P.R. China.

出版信息

Mol Med Rep. 2017 Dec;16(6):8045-8054. doi: 10.3892/mmr.2017.7653. Epub 2017 Sep 28.

Abstract

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.

摘要

非编码 RNA(ncRNA),如 microRNA(miRNA)和长链非编码 RNA(lncRNA),在涉及疾病发展的病理过程中发挥着越来越重要的作用。然而,mRNA 是否与 miRNA 和 lncRNA 相互作用形成疾病中的相互调节网络尚不清楚。在这项研究中,系统性地分析了人肺泡上皮细胞中肿瘤生长因子-β1 激活(TGF-β1)上皮-间充质转化(EMT)过程中 coexpressed mRNAs、miRNAs 和 lncRNAs 的相互作用。对于 EMT 调控,24 个 mRNAs、11 个 miRNAs 和 33 个 lncRNAs 共表达并相互作用。进一步分析了 coexpressed mRNAs、miRNAs 和 lncRNAs 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其他模式相关,如组蛋白修饰和转录因子募集。然而,由于 lncRNAs 的普遍低丰度和蛋白质-RNA 相互作用的频繁混杂,不能忽视 ceRNA 存在的可能性。因此,结论需要进一步的实验鉴定和验证。在这种情况下,破坏许多改变的疾病途径仍然是获得有效基于途径的治疗的挑战之一。原因是一个特定的 mRNA、miRNA 或 lncRNA 可能靶向多个可能与疾病有关的基因。尽管如此,本研究的结果为疾病,特别是肺部肿瘤和纤维化提供了基本的机制信息、可能的生物标志物和新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83d3/5779888/a2f01faa364d/MMR-16-06-8045-g01.jpg

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