Qian Zhang1,2,3,4, Tianxiang Ni1,2,3,4, Yujie Dang1,2,3,4, Lingling Ding1,2,3,4, Jingjing Jiang1,2,3,4, Jing Li1,2,3,4, Mingdi Xia1,2,3,4, Na Yu1,2,3,4, Jinlong Ma1,2,3,4, Junhao Yan5,6,7,8, Zi-Jiang Chen1,2,3,4,9,10. 1. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, No. 157 Jingliu Road, Jinan, 250012, Shandong, China. 2. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, Shandong, China. 3. Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, Shandong, China. 4. Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, 250012, Shandong, China. 5. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, No. 157 Jingliu Road, Jinan, 250012, Shandong, China. yyy306@126.com. 6. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, Shandong, China. yyy306@126.com. 7. Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, Shandong, China. yyy306@126.com. 8. Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, 250012, Shandong, China. yyy306@126.com. 9. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetic, Shanghai, 200127, China. 10. Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
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-148a-3p 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.
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-148a-3p 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.
Authors: Christos Coutifaris; Evan R Myers; David S Guzick; Michael P Diamond; Sandra A Carson; Richard S Legro; Peter G McGovern; William D Schlaff; Bruce R Carr; Michael P Steinkampf; Susan Silva; Donna L Vogel; Phyllis C Leppert Journal: Fertil Steril Date: 2019-10 Impact factor: 7.329
Authors: Youn-Jung Kang; Miranda Lees; Laura C Matthews; Susan J Kimber; Karen Forbes; John D Aplin Journal: J Cell Sci Date: 2015-01-20 Impact factor: 5.285