hsa-miR-100-5p, an overexpressed miRNA in human ovarian endometriotic stromal cells, promotes invasion through attenuation of SMARCD1 expression
hsa-miR-100-5p, an overexpressed miRNA in human ovarian endometriotic stromal cells, promotes invasion through attenuation of SMARCD1 expression
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DOI：
10.1186/s12958-020-00590-3
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发表时间：
2020-04-16
影响因子：
4.4
通讯作者：
Narahara, Hisashi
中科院分区：
文献类型：
--
作者：
Takebayashi, Kanetoshi;Nasu, Kaei;Narahara, Hisashi
背景：子宫内膜异位症中大量microRNA表达异常，并参与其发病机制。我们先前的研究表明，has-miR-100- 5 p在人增生性囊肿基质细胞（ECSC）中的表达增强。本研究旨在探讨has-miR-100- 5 p在子宫内膜异位症发病机制中的作用。利用转染hsa-miR-100- 5 p的NESC，通过Transwell侵袭实验和体外创伤修复实验评价hsa-miR-100- 5 p对NESC侵袭能力的影响。结果：转染hsa-miR-100 - 5 p后，NES细胞的侵袭能力和运动能力均明显增强。hsa-miR-100- 5 p转染后，SWItch/蔗糖非发酵相关基质相关肌动蛋白依赖性染色质亚家族D成员调节因子1（SMARD 1）的mRNA表达显著减弱。结论：SMARD 1/MMP-1是hsa-miR-100- 5 p的下游通路。hsa-miR-100- 5 p转染通过抑制SMARD 1表达和MMP 1活化增强NESC的运动性。这些发现表明，hsa-miR-100- 5 p在子宫内膜异位症中的表达增强参与促进子宫内膜异位症特异性特征的获得。因此，我们目前对hsa-miR-100- 5 p作用的研究结果可能有助于了解子宫内膜异位症发病机制中的表观遗传学机制。
Background: A number of microRNAs are aberrantly expressed in endometriosis and are involved in its pathogenesis. Our previous study demonstrated that has-miR-100-5p expression is enhanced in human endometriotic cyst stromal cells (ECSCs). The present study aimed to elucidate the roles of has-miR-100-5p in the pathogenesis of endometriosis.Methods: Normal endometrial stromal cells (NESCs) were isolated from normal eutopic endometrium without endometriosis. Using hsa-miR-100-5p-transfected NESCs, we evaluated the effect of hsa-miR-100-5p on the invasiveness of these cells by Transwell invasion assay and in-vitro wound repair assay. We also investigated the downstream signal pathways of hsa-miR-100-5p by microarray analysis and Ingenuity pathways analysis.Results: hsa-miR-100-5p transfection enhanced the invasion and motility of NESCs. After hsa-miR-100-5p transfection, mRNA expression of SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (SMARCD1) was significantly attenuated. Whereas, the expression of matrix metallopeptidase 1 (MMP1) mRNA and active MMP1 protein levels was upregulated.Conclusion: We found that SMARCD1/MMP-1 is a downstream pathway of hsa-miR-100-5p. hsa-miR-100-5p transfection enhanced the motility of NESCs by inhibiting SMARCD1 expression and MMP1 activation. These findings suggest that enhanced hsa-miR-100-5p expression in endometriosis is involved in promoting the acquisition of endometriosis-specific characteristics during endometriosis development. Our present findings on the roles of hsa-miR-100-5p may thus contribute to understand the epigenetic mechanisms involved in the pathogenesis of endometriosis.