MicroRNA-181a is involved in the regulation of human endometrial stromal cell decidualization by inhibiting Krüppel-like factor 12

Qun Zhang, Hui Zhang, Yue Jiang, Bai Xue, Zhenyu Diao, Lijun Ding, Xin Zhen, Haixiang Sun, Guijun Yan, Yali Hu

The transformation of endometrium into decidua is essential for normal implantation of the blastocyst. However, the post-transcriptional regulation and the miRNAs involved in decidualization remain poorly understood. Here, we examined microRNA-181a (miR-181a) expression in decidualized human endometrial stromal cell (hESC). In addition, we investigated the functional effect of miR-181a on hESC decidualization in vitro. Quantitative real-time PCR (qRT-PCR) was used to detect the profile of miR-181a in decidualized hESC. qRT-PCR, enzyme-linked fluorescent assay, and immunofluorescence assay were performed to investigate decidualization marker genes' expression after enhancing or inhibition of miR-181a expression in hESC. Luciferase reporter assay, western blotting, qRT-PCR, and immunofluorescence assay were carried out to identify the relationship between miR-181a and Krüppel-like factor 12 (KLF12). miR-181a expression levels increased dramatically in hESC treated with 8-Br-cAMP and MPA. Increased miR-181a expression promoted hESC decidualization-related gene expression and morphological transformation; conversely, inhibition of miR-181a expression compromised hESC decidualization in vitro. Further analysis confirmed that miR-181a interacted with the 3' untranslated region of the transcription factor KLF12 and down-regulated KLF12 at the transcriptional and translational levels. KLF12 overexpression abolished miR-181a-induced decidualization. Our findings suggest that miR-181a plays a functionally important role in human endometrial stromal cell decidualization in vitro by inhibiting KLF12.