BACKGROUND Recent advances in the functional analyses of endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs), have provided a new perspective on the crucial roles of RNA in gene regulation. Consequently, LncRNA deregulation is a key factor in various diseases, including pulmonary disorders like Cystic Fibrosis (CF). CF is the most common life limiting recessive disease in the U.S., and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction. METHODS Here we report a distinct LncRNA signature and corresponding mRNAs that distinguishes CF lung (airway and parenchyma) tissues from matched non-CF controls (n = 4 each group), generated by microarray specific for LncRNAs which includes corresponding mRNA expressions. In silico analyses of the cellular processes that are impacted by these LncRNAs was performed using Gene Ontology (GO). A selected subset of LncRNAs were validated by quantitative real-time PCR. RESULTS We have identified 636 LncRNAs differentially expressed in CF airway epithelium and 1974 in CF lung parenchyma compared to matched non-CF controls (fold change ≥2, p < 0.05), majority of which (> 50%) are intergenic. Interestingly, 15 of these differentially expressed LncRNAs and 9 coding mRNAs are common to airway and parenchyma tissues. GO analyses indicates that signaling pathways and cell membrane functions are significantly affected by the alteration in LncRNA expressions in CF lung tissues. Seven of the differentially expressed LncRNAs, exhibit similar expression trends in CFBE41o- compared to control cells. CONCLUSION Understanding the mechanisms by which these LncRNAs regulate CF disease phenotype will help develop novel therapeutic targets for CF and related pulmonary diseases, such as COPD and Asthma.

中文翻译：

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囊性纤维化肺气道和实质组织中体内长非编码RNA分布的比较分析。

背景技术内源性非编码RNA（ncRNA）分子，包括长非编码RNA（LncRNA）的功能分析的最新进展，为RNA在基因调控中的关键作用提供了新的视角。因此，LncRNA的失调是多种疾病（包括肺部疾病，如囊性纤维化（CF））的关键因素。CF是美国最常见的限制生命的隐性疾病，归因于CFTR基因的突变。CF突变（最常见的是F508del-CFTR）阻止突变CFTR蛋白的正确折叠，运输和功能，并进一步通过促炎性细胞因子和趋化因子过度表达进入气管腔而导致支气管扩张和最终形成在肺部破坏。方法在这里，我们报告了一个独特的LncRNA签名和相应的mRNA，它们将CF肺（气道和实质）组织与匹配的非CF对照（每组n = 4）区分开来，后者由LncRNA特异的微阵列产生，包括相应的mRNA表达。使用基因本体论（GO）对受这些LncRNA影响的细胞过程进行了计算机分析。通过定量实时PCR验证了所选的LncRNA的子集。结果与匹配的非CF对照相比，我们已经鉴定出636个LncRNA在CF气道上皮中差异表达，1974年在CF肺实质中差异表达（倍数变化≥2，p <0.05），其中大多数（> 50％）是基因间的。有趣的是，这些差异表达的LncRNA中有15个和9个编码mRNA在气道和实质组织中很常见。GO分析表明，CF肺组织中LncRNA表达的改变显着影响信号通路和细胞膜功能。与对照细胞相比，七种差异表达的LncRNA在CFBE410中表现出相似的表达趋势。结论了解这些LncRNA调控CF疾病表型的机制将有助于开发针对CF和相关肺部疾病（如COPD和哮喘）的新型治疗靶标。