MiR-148a-3p may contribute to flawed decidualization in recurrent implantation failure by modulating HOXC8
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REPRODUCTIVE PHYSIOLOGY AND DISEASE
MiR-148a-3p may contribute to flawed decidualization in recurrent implantation failure by modulating HOXC8 Qian Zhang 1,2,3,4 & Tianxiang Ni 1,2,3,4 & Yujie Dang 1,2,3,4 & Lingling Ding 1,2,3,4 & Jingjing Jiang 1,2,3,4 & Jing Li 1,2,3,4 & Mingdi Xia 1,2,3,4 & Na Yu 1,2,3,4 & Jinlong Ma 1,2,3,4 & Junhao Yan 1,2,3,4 & Zi-Jiang Chen 1,2,3,4,5,6 Received: 12 February 2020 / Accepted: 21 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose To evaluate whether miR-148a-3p overexpression is associated with disrupted decidualization of recurrent implantation failure (RIF). Methods Endometrial miRNA and mRNA expression profiles during the implantation window derived from women with and without RIF were identified using microarray and RT-qPCR. Immortalized human endometrial stromal cells (HESCs) were cultured for proliferation and in vitro decidualization assays after enhancing miR-148a-3p expression or inhibiting putative target gene homeobox C8 (HOXC8) expression. RT-qPCR, western blot, and luciferase reporter assays were used to confirm the relationship between miR-148a-3p and HOXC8 gene. Results MiR-148a-3p was significantly upregulated in RIF endometrial tissues. Forced expression of miR-148a-3p notably attenuated HESC in vitro decidualization. Mechanistic studies revealed that miR-148a-3p directly bounds to the HOXC8 3′ untranslated region (3′UTR) and suppressed HOXC8 expressions in both mRNA and protein levels. Further investigations demonstrated that inhibition of HOXC8 in HESCs induced similar effects on decidual process as those induced by miR-148a3p overexpression. Conclusion Taken together, our findings suggested that elevated miR-148a-3p might account for flawed decidualization in RIF by negatively regulating HOXC8, raising the possibility that miR-148a-3p might be a novel therapeutic target in RIF. Keywords Recurrent implantation failure . Decidualization . miR-148a-3p . HOXC8
Introduction Despite impressive advances in in vitro fertilization-embryo transfer (IVF-ET) and its derivative techniques, there are still many infertile couples suffering from recurrent implantation
failure (RIF). RIF, defined as failure to achieve a clinical pregnancy following more than three transfers with high-quality embryos or the transfer of ten or more embryos in multiple cycles, is an intriguing clinical dilemma in human-assisted reproduction treatment [1, 2]. Although the underlying
Qian Zhang and Tianxiang Ni contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10815-020-01900-9) contains supplementary material, which is available to authorized users. * Junhao Yan [email protected] 1
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Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, No. 157 Jingliu Road, Jinan 250012, Shandong, China National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan 250012, Shandong, China
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