Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis.
Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis.
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分析lncRNA与蛋白编码基因的关系以及lncRNA作为ceRNA在肺纤维化中的作用
DOI：
10.1111/jcmm.12243
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发表时间：
2014-06
影响因子：
5.3
通讯作者：
Lv C
中科院分区：
文献类型：
--
作者：
Song X;Cao G;Jing L;Lin S;Wang X;Zhang J;Wang M;Liu W;Lv C
长链非编码RNA（lncRNA）参与多种病理生理过程和人类疾病。然而，其动力学和相应的功能在肺纤维化仍然知之甚少。在这项研究中，部分lncRNA邻近或同源的蛋白质编码基因，确定通过搜索UCSC基因组生物信息学数据库。发现这对于探索lncRNA在疾病进展中的功能是潜在有用的。以往的研究表明竞争性内源RNA（ceRNA）假说是预测lncRNA功能的另一种方法。然而，关于ceRNA在肺纤维化中的功能知之甚少。本研究选取了两个差异表达的lncRNAs MRAK 088388和MRAK 081523，探讨其调控机制。将MRAK 088388和MRAK 081523作为长基因间非编码RNA（lincRNA）进行分析，并分别鉴定为小鼠lncRNA AK 088388和AK 081523的直向同源物。qRT-PCR和原位杂交（ISH）结果显示，它们在肺间质细胞中表达明显上调，并定位于细胞质中。我们还发现，MRAK 088388和N4 bp 2对miR-200、miR-429、miR-29和miR-30具有相同的miRNA反应元件（MRE），而MRAK 081523和Plxna 4对miR-218、miR-141、miR-98和let-7具有相同的MRE。此外，N4 bp 2和Plxna 4的表达水平在纤维化大鼠中显著增加，并且分别与MRAK 088388和MRAK 081523的表达水平高度相关。在它们共有的miRNAs中，miR-29 b-3 p和let-7 i-5 p在模型组表达降低，并分别与MRAK 088388和MRAK 081523的表达呈负相关。MRAK 088388和MRAK 081523分别通过海绵状作用于miR-29 b-3 p和let-7i-5 p来调控N4 bp 2和Plxna 4的表达，具有ceRNA的调控功能。因此，我们的研究可能为深入了解lncRNA、miRNA和mRNA之间的功能相互作用，为肺纤维化的发病机制和治疗提供新的理论依据。
Long non-coding RNAs (lncRNAs) are involved in various pathophysiologic processes and human diseases. However, their dynamics and corresponding functions in pulmonary fibrosis remain poorly understood. In this study, portions of lncRNAs adjacent or homologous to protein-coding genes were determined by searching the UCSC genome bioinformatics database. This was found to be potentially useful for exploring lncRNA functions in disease progression. Previous studies showed that competing endogenous RNA (ceRNA) hypothesis is another method to predict lncRNA function. However, little is known about the function of ceRNA in pulmonary fibrosis. In this study, we selected two differentially expressed lncRNAs MRAK088388 and MRAK081523 to explore their regulatory mechanisms. MRAK088388 and MRAK081523 were analysed as long-intergenic non-coding RNAs (lincRNAs), and identified as orthologues of mouse lncRNAs AK088388 and AK081523, respectively. qRT-PCR and in situ hybridization (ISH) showed that they were significantly up-regulated, and located in the cytoplasm of interstitial lung cells. We also showed that MRAK088388 and N4bp2 had the same miRNA response elements (MREs) for miR-200, miR-429, miR-29, and miR-30, whereas MRAK081523 and Plxna4 had the same MREs for miR-218, miR-141, miR-98, and let-7. Moreover, the expression levels of N4bp2 and Plxna4 significantly increased in fibrotic rats, and were highly correlated with those of MRAK088388 and MRAK081523, respectively. Among their shared miRNAs, miR-29b-3p and let-7i-5p decreased in the model group, and were negatively correlated with the expression of MRAK088388 and MRAK081523, respectively. MRAK088388 and MRAK081523 could regulate N4bp2 and Plxna4 expression by sponging miR-29b-3p and let-7i-5p, respectively, and possessed regulatory functions as ceRNAs. Thus, our study may provide insights into the functional interactions of lncRNA, miRNA and mRNA, and lead to new theories for the pathogenesis and treatment of pulmonary fibrosis.