Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis
Regulatory network of two circRNAs and an miRNA with their targeted genes under astilbin treatment in pulmonary fibrosis
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落新妇苷治疗肺纤维化过程中两个 circRNA 和一个 miRNA 及其靶基因的调控网络
DOI：
10.1111/jcmm.14550
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发表时间：
2019-10-01
影响因子：
5.3
通讯作者：
Song, Xiaodong
中科院分区：
文献类型：
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作者：
Lu, Guangping;Zhang, Jinjin;Song, Xiaodong
环状RNA（CircRNA）正在成为新的治疗药物靶点。然而，在落新妇苷治疗下，它们的概况尚未报道。在这项研究中，我们分析了肺纤维化中落新妇苷治疗下circRNA转录组的全局重编程和circRNA及其靶基因的调控网络。使用RNA测序，与博来霉素治疗组相比，落新妇苷治疗组中共有145个circRNA差异表达。博来霉素和落新妇苷处理组共检测到29条circRNA，其中第2号染色体上的circRNA数量最多，长度变化主要集中在1000 bp以内。检测了四种差异表达的circRNA（circRNA-662、949、394和986）以验证RNA测序数据，并通过qRT-PCR、Western blot、Pearson相关系数、双荧光素酶报告系统和抗AGO 2 RNA免疫沉淀分析了其靶向microRNA和基因。结果表明，circRNA-662和949可以作为靶向Gli 2和STAT 3的“miR-29 b海绵”发挥其功能。我们的工作表明落新妇苷处理下circRNA水平的转录组复杂性。这些circRNA可能是药物作用的潜在分子靶点。
Circular RNAs (circRNAs) are becoming new therapeutic drug targets. However, their profiles under astilbin treatment have not been reported yet. In this study, we analysed the global reprogramming of circRNA transcriptome and a regulatory network of circRNAs with their targeted genes under astilbin treatment in pulmonary fibrosis. A total of 145 circRNAs were differentially expressed in the astilbin‐treated group compared with the bleomycin‐treated group using RNA sequencing. In the bleomycin‐ and astilbin‐treated groups, 29 coexpressed circRNAs were found. The maximum number of circRNAs was distributed on chromosome two, and their length varieties were mainly within 1000 bp. Four differentially expressed circRNAs (circRNA‐662, 949, 394 and 986) were tested to validate the RNA sequencing data, and their targeted microRNAs and genes were analysed by qRT‐PCR, Western blot, Pearson correlation coefficient, a dual‐luciferase reporter system and anti‐AGO2 RNA immunoprecipitation. The results showed that circRNA‐662 and 949 can act as “miR‐29b sponges” targeting Gli2 and STAT3 to exert their functions. Our work suggests that the transcriptome complexity at the circRNA level under astilbin treatment. These circRNAs may be potential molecular targets for drug action.