Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.

Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.
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环状RNA在特发性肺纤维化中的潜在调节作用

DOI:
10.3892/ijmm.2018.3892
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发表时间:
2018-12
影响因子:
5.4
通讯作者:
Lv C
Lv C
中科院分区:
医学3区
文献类型:
--
作者:
Li R;Wang Y;Song X;Sun W;Zhang J;Liu Y;Li H;Meng C;Zhang J;Zheng Q;Lv C

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特发性肺纤维化(IPF)是一种慢性进行性间质性肺炎,病因不明,预后差,无有效治疗方法。环状RNA (circRNAs)作为潜在的治疗靶点和某些疾病的诊断性生物标志物,是近年来RNA研究领域的一个热点。在本研究中,通过circRNA微阵列技术,在IPF患者血浆中共鉴定出67个显著失调的circRNA。在这些环状rna中,38个被上调,29个被下调。聚合酶链反应进一步验证结果表明,与健康对照相比,IPF患者血浆样本中hsa _circRNA_100906、hsa_circRNA_102100和hsa_circRNA_102348的表达水平显著上调,而hsa_circRNA_101225、hsa_circRNA_104780和hsa_circRNA_101242的表达水平下调。大多数差异表达的环状rna是由外显子区产生的。差异表达circRNAs的宿主基因参与细胞周期、粘附连接和RNA转运的调控。环状RNA /微RNA /mRNA相互竞争的内源性RNA (ceRNA)网络表明,受环状RNA保护的mRNA参与了转化生长因子-β1、缺氧诱导因子-1、Wnt、Janus激酶、rho相关蛋白激酶、血管内皮生长因子、丝裂原活化蛋白激酶、Hedgehog和核因子κB信号通路或作为肺纤维化的生物标志物。此外,荧光素酶报告基因检测证实,hsa_circRNA_100906和hsa_circRNA_102348分别直接与miR-324-5p和miR-630相互作用,这两种基因在IPF患者中下调。本研究为探索IPF疾病的潜在分子机制提供了新的途径。
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive type of interstitial pneumonia with unknown causes, poor prognosis and no effective therapy available. Circular RNAs (circRNAs), which serve as potential therapeutic targets and diagnostic biomarkers for certain diseases, represent a recent hotspot in the field of RNA research. In the present study, a total of 67 significantly dysregulated circRNAs were identified in the plasma of IPF patients by using a circRNA microarray. Among these circRNAs, 38 were upregulated, whereas 29 were downregulated. Further validation of the results by polymerase chain reaction analysis indicated that Homo sapiens (hsa)_circRNA_100906, hsa_circRNA_102100 and hsa_circRNA_102348 were significantly upregulated, whereas hsa_circRNA_101225, hsa_circRNA_104780 and hsa_circRNA_101242 were downregulated in plasma samples of IPF patients compared with those in samples from healthy controls. The majority of differentially expressed circRNAs were generated from exonic regions. The host genes of the differentially expressed circRNAs were involved in the regulation of the cell cycle, adherens junctions and RNA transport. The competing endogenous RNA (ceRNA) network of the circRNAs/micro(mi)RNAs/mRNAs indicated that circRNA-protected mRNA participated in transforming growth factor-β1, hypoxia-inducible factor-1, Wnt, Janus kinase, Rho-associated protein kinase, vascular endothelial growth factor, mitogen-activated protein kinase, Hedgehog and nuclear factor κB signalling pathways or functioned as biomarkers for pulmonary fibrosis. Furthermore, luciferase reporter assays confirmed that hsa_circRNA_100906 and hsa_circRNA_102348 directly interact with miR-324-5p and miR-630, respectively, which were downregulated in IPF patients. The present study provided a novel avenue for exploring the underlying molecular mechanisms of IPF disease.
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