Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway.
Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway.
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DOI：
10.3892/ol.2018.7910
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发表时间：
2018-04
期刊：
影响因子：
2.9
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Du Y;Hao X;Liu X
本研究旨在探讨细胞周期蛋白依赖性激酶抑制剂2B反义RNA 1（CDKN 2B-AS 1）在特发性肺纤维化（IPF）患者外周血中的表达。共纳入24例IPF患者和24例健康对照，随机选择4例IPF患者和4例健康对照提取RNA。两组均无高血压、糖尿病等其他疾病。从外周血中提取RNA，高通量测序，并进行生物信息学分析。根据筛选出的差异表达的lncRNA和mRNA，进行基因本体分析以筛选出肿瘤相关的mRNA。共选择了20个样本，以避免由于个体差异导致的方差。共20例IPF患者和20例对照者进一步研究，从外周血中提取RNA用于验证lncRNA和mRNA水平。根据差异表达筛选结果，共鉴定出440个lncRNA上调，1，376个下调。高通量测序和生物信息学分析表明，与健康对照相比，IPF患者中CDKN 2B-AS 1的表达显著降低。CDKN 2B-AS 1的相邻基因mRNA被鉴定为CDKN 2A，根据京都基因和基因组百科全书数据库，其是一个重要的抑癌基因，集中在p53信号通路上。CDKN 2A mRNA表达水平在IPF患者中较低，而在对照组中较高。IPF组CDKN 2B-AS 1和CDKN 2A mRNA表达均低于对照组（P<0.05）。结果表明，CDKN 2B-AS 1和邻近基因CDKN 2A的表达在IPF患者的外周血中下调，其激活p53信号通路以促进肺癌形成。
The present study aimed to investigate the expression of long non-coding RNA (lncRNA) cyclin dependent kinase inhibitor-2B-antisense RNA 1 CDKN2B-AS1 in patients with peripheral blood of idiopathic pulmonary fibrosis (IPF). A total of 24 patients with IPF and 24 healthy controls were included in the study, four patients with IPF and four healthy controls were selected randomly to extract RNA. There were no other diseases such as hypertension and diabetes in the two groups. RNA from peripheral blood was extracted by high-throughput sequencing and bioinformatics analysis was performed. Based on selected differentially expressed lncRNA and mRNA, gene ontology analysis was performed to screen out the tumor-associated mRNA. A total of 20 samples were chosen to avoid variance due to individual differences. A total of 20 patients with IPF, and 20 controls were further studied, RNA extracted from peripheral blood was used to verify the lncRNA and mRNA levels. A total of 440 lncRNAs were identified to be upregulated and 1,376 downregulated according to the screening results of differential expression. High-throughput sequencing and bioinformatics analysis demonstrated that the expression of CDKN2B-AS1 decreased significantly in patients with IPF compared with healthy controls. The adjacent gene mRNA of CDKN2B-AS1 was identified as CDKN2A, an important anti-oncogene, which is concentrated on the p53 signaling-pathway according to the Kyoto Encyclopedia of Genes and Genomes database. CDKN2A mRNA expression levels were lower in patients with IPF and higher in the control group. The expression of CDKN2B-AS1 and CDKN2A mRNA was significantly lower in IPF group compared with in the control group (P<0.05). The results suggest the expression of the CDKN2B-AS1 and adjacent gene, CDKN2A, are downregulated in the peripheral blood of patients with IPF, which activates the p53-signaling pathway to promote lung cancer formation.