circFAM120A participates in repeated implantation failure by regulating decidualization via the miR-29/ABHD5 axis
circFAM120A participates in repeated implantation failure by regulating decidualization via the miR-29/ABHD5 axis
复制标题
circFAM120A 通过 miR-29 / ABHD5 轴调节蜕膜化参与反复着床失败
DOI：
10.1096/fj.202002298rr
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发表时间：
2021-09-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Zi-Jiang
中科院分区：
文献类型：
--
作者：
Zhou, Tingting;Ni, Tianxiang;Chen, Zi-Jiang
重复着床失败（RIF）是限制与辅助生殖技术相关的妊娠率的主要问题。然而，RIF的发病机制尚不清楚。最近，环状rna （circRNAs）的表达水平在RIF患者的子宫内膜组织中被分析。然而，circrna在RIF中的确切作用尚不清楚。在我们的研究中，我们发现与非RIF对照组相比，RIF患者着床窗期子宫内膜中cirfam120a水平显著下调。抑制cirfam120a表达可抑制人子宫内膜间质细胞（hESCs）的去细胞化。此外，circFAM120A敲低后的RNA-seq分析显示ABHD5是circFAM120A的潜在下游靶基因。正如预期的那样，下调hESCs中的ABHD5也抑制了去个化。利用starBase和TargetScan数据库，基于核苷酸序列匹配，我们预测miR-29可能与ABHD5相互作用。荧光素酶报告基因检测显示，miR-29在预测的互补位点与ABHD5的3 ' UTR结合。此外，miR-29模拟物有效地降低了ABHD5的表达水平并抑制了脱偶化过程，而miR-29抑制剂通过敲低circFAM120A部分地挽救了ABHD5 mRNA的表达水平和脱偶化。因此，cirfam120a通过miR-29/ABHD5轴调节RIF的去个性化。
Repeated implantation failure (RIF) is a major problem that limits the pregnancy rate associated with assisted reproductive technology. However, the pathogenesis of RIF is still unknown. Recently, the expression levels of circular RNAs (circRNAs) were profiled in the endometrial tissues of patients with RIF. However, the exact role of circRNAs in RIF remains unclear. In our study, we found that circFAM120A levels were significantly down-regulated in the endometrium at the window of implantation in RIF patients compared with non-RIF controls. The suppression of circFAM120A expression inhibited decidualization in human endometrial stromal cells (hESCs). Furthermore, RNA-seq analysis after circFAM120A knockdown revealed ABHD5 as a potential downstream target gene of circFAM120A. As expected, down-regulating ABHD5 in hESCs also inhibited decidualization. Using the starBase and TargetScan databases, we predicted that miR-29 may interact with ABHD5, based on nucleotide sequence matching. Luciferase reporter assay showed that miR-29 bound to the 3 ' UTR of ABHD5 at the predicted complementary sites. Moreover, miR-29 mimics efficiently reduced ABHD5 expression levels and suppressed the decidualization process, whereas a miR-29 inhibitor partly rescued ABHD5 mRNA expression level and decidualization reduced by the knockdown of circFAM120A. Therefore, circFAM120A modulated decidualization in RIF through the miR-29/ABHD5 axis.