Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.

Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.
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microRNA 和 mRNA 配对表达谱的整合分析确定了卵巢子宫内膜异位症中失调的 microRNA-转录因子-基因调控网络。

DOI:
10.1186/s12958-017-0319-5
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发表时间:
2018-01-22
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Meng Y
Meng Y
中科院分区:
其他
文献类型:
--
作者:
Zhao L;Gu C;Ye M;Zhang Z;Li L;Fan W;Meng Y

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子宫内膜异位症的病因和病理生理尚不清楚。越来越多的证据表明,microRNA (miRNA)和转录因子(TF)的异常表达可能参与了子宫内膜异位症的发病和发展。因此,本研究旨在调查关键mirna、tf和基因,进一步了解子宫内膜异位症的发病机制。采用高通量测序技术测定了8例卵巢子宫内膜异位症患者异位子宫内膜与同位子宫内膜中miRNA和mRNA的配对表达谱。通过Pearson相关系数鉴定mirna、tf和相应基因之间的二元相互作用和回路。利用生物信息学方法构建mirna - tf基因调控网络。通过定量逆转录聚合酶链反应对22例患者的11个选定的mirna和tf进行验证。总体而言,通过比较异位子宫内膜组和异位子宫内膜组的测序,共鉴定出107种差异表达的mirna和6112种差异表达的mrna。mirna - tf基因调控网络由22个mirna、12个tf和430个相应基因组成。具体来说,来自miR-449和miR-34b/c集群、miR-200家族、miR-106a-363集群、miR-182/183、FOX家族、GATA家族和E2F家族以及CEBPA、SOX9和HNF4A的一些关键调控因子被认为在子宫内膜异位症的发病过程中发挥重要的调节作用。miRNA和mRNA表达谱的整合分析为这种神秘疾病的调控网络提供了独特的见解,并可能为子宫内膜异位症的替代治疗提供线索。本文的在线版本(10.1186/s12958-017-0319-5)包含补充材料,授权用户可使用。
The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients. Overall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis. Integration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis. The online version of this article (10.1186/s12958-017-0319-5) contains supplementary material, which is available to authorized users.
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