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miRNA 和 mRNA 配对表达谱的整合分析鉴定出卵巢子宫内膜异位症中失调的 miRNA-转录因子-基因调控网络。

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

机构信息

Department of Gynecology and Obstetrics, People's Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853, China.

Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing, China.

出版信息

Reprod Biol Endocrinol. 2018 Jan 22;16(1):4. doi: 10.1186/s12958-017-0319-5.

DOI:10.1186/s12958-017-0319-5
PMID:29357938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5776778/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

子宫内膜异位症的病因和病理生理学仍不清楚。越来越多的证据表明,异常的 microRNA(miRNA)和转录因子(TF)表达可能参与子宫内膜异位症的发病机制和发展。因此,本研究旨在调查关键的 miRNA、TF 和基因,并进一步了解子宫内膜异位症的发病机制。

方法

通过高通量测序技术,在 8 名卵巢子宫内膜异位症患者中比较异位内膜和在位内膜的 miRNA 和 mRNA 表达谱。通过 Pearson 相关系数确定 miRNA、TF 和相应基因之间的二元相互作用和电路。使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在 22 名患者中验证 11 个选定的 miRNA 和 TF。

结果

通过比较异位内膜组和在位内膜组的测序,共鉴定出 107 个差异表达的 miRNA 和 6112 个差异表达的 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。具体而言,miR-449 和 miR-34b/c 簇、miR-200 家族、miR-106a-363 簇、miR-182/183、FOX 家族、GATA 家族、E2F 家族以及 CEBPA、SOX9 和 HNF4A 等一些关键调节剂被认为在子宫内膜异位症的发病机制中发挥着重要的调节作用。

结论

miRNA 和 mRNA 表达谱的综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疗法提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/a3ee8e18a152/12958_2017_319_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/7f75dbdb1858/12958_2017_319_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/68504aa554aa/12958_2017_319_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/21c0b6cf48d3/12958_2017_319_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/a3ee8e18a152/12958_2017_319_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/7f75dbdb1858/12958_2017_319_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/68504aa554aa/12958_2017_319_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/21c0b6cf48d3/12958_2017_319_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f29/5776778/a3ee8e18a152/12958_2017_319_Fig4_HTML.jpg

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