Long non-coding RNA MALAT1 protects preterm infants with bronchopulmonary dysplasia by inhibiting cell apoptosis
Long non-coding RNA MALAT1 protects preterm infants with bronchopulmonary dysplasia by inhibiting cell apoptosis
复制标题
长非编码RNA MALAT1通过抑制细胞凋亡保护支气管肺发育不良早产儿
DOI：
10.1186/s12890-017-0524-1
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发表时间：
2017-12-13
影响因子：
3.1
通讯作者：
Gong, Xiaohui
中科院分区：
文献类型：
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作者：
Cai, Cheng;Qiu, Jiajun;Gong, Xiaohui
背景：支气管肺发育不良（BPD）是一种以早产儿肺泡发育受损为特征的新生儿慢性肺病。到目前为止，对BPD的分子和细胞基础知之甚少。越来越多的证据表明lncRNAs在肺器官发生过程中调控细胞增殖和凋亡。lncrna在BPD发病机制中的潜在作用尚不清楚。本研究旨在阐明MALAT1在早产儿BPD发病过程中的作用，阐明MALAT1参与早产儿的保护作用。方法通过重新分析基因表达数据库gene expression omnibus （GEO）中的数据集GSE25286 （Mouse GEO Genome 4302 Array）来评估MALAT1在BPD小鼠肺组织中的表达，并通过实时q-PCR验证MALAT1在BPD患者肺组织中的表达。然后通过分析数据集GSE43830检测MALAT1在调节细胞生物学中的作用。CDC6是一种已知的抗凋亡基因，在BPD患者和MALAT1被敲低的肺泡上皮细胞系A549细胞中得到了证实。采用PI/Annexin-V染色，流式细胞仪检测细胞凋亡。结果与WT相比，BPD小鼠肺组织中MALAT1在第14天和第29天的表达均有显著差异（P< 0.05）。与mRNA阵列分析结果一致，BPD早产儿血液样本中MALAT1表达水平显著升高。对WI-38细胞MALAT1敲低的生物信息学数据分析显示，凋亡相关通路中富集了多种差异表达基因。q-PCR结果进一步证实抗凋亡基因CDC6表达下调。PI/Annexin-V凋亡实验结果显示，MALAT1在肺泡上皮细胞系（A549）中下调可促进细胞凋亡。结论在我们的研究中，我们发现上调lncRNA MALAT1可以通过抑制细胞凋亡来保护BPD早产儿。这些数据为MALAT1调控提供了新的见解，它可能与细胞命运有关，并为BPD的预防和治疗提供了线索。
BackgroundBronchopulmonary dysplasia (BPD) is a neonatal chronic lung disease characterized by impaired pulmonary alveolar development in preterm infants. Until now, little is known about the molecular and cellular basis of BPD. There is increasing evidence that lncRNAs regulate cell proliferation and apoptosis during lung organogenesis. The potential role of lncRNAs in the pathogenesis of BPD is unclear. This study aims to clarify the role of MALAT1 during the process of BPD in preterm infants and illustrate the protective effect of MALAT1 involved in preterm infants.MethodsWe assessed the expression of MALAT1 in BPD mice lung tissues by reanalyzing dataset GSE25286 (Mouse GEO Genome 4302 Array) from gene expression database gene expression omnibus (GEO), and verified MALAT1 expression in BPD patients by realtime q-PCR. Then the role of MALAT1 in regulating cell biology was examined by profiling dataset GSE43830. The expression of CDC6, a known antiapoptopic gene was verified in BPD patients and the alveolar epithelial cell line A549 cells in which MALAT1 was knocked down. Cell apoptosis was determined by FACS using PI/Annexin-V staining.ResultsThe expression of MALAT1 was significantly evaluated in lung tissues of BPD mice at day 14 and day 29 compared to WT (P< 0.05). In consistent with mRNA array profiling analysis, MALAT1 expression level in blood samples from preterm infants with BPD was significantly increased. Bioinformative data analysis of MALAT1 knockdown in WI-38 cells showed various differentially expressed genes were found enriched in apoptosis related pathway. Down-regulation of antiapoptopic gene, CDC6 expression was further verified by q-PCR result. PI/Annexin-V apoptisis assay results showed that MALAT1 knocked down in the alveolar epithelial cell line (A549) promotes cell apoptosis.ConclusionsIn our study, we found that up-regulation of lncRNA MALAT1 could protect preterm infants with BPD by inhibiting cell apoptosis. These data provide novel insights into MALAT1 regulation which may be relevant to cell fate and shed light on BPD prevention and treatment.