MiR-148a-3p May Contribute to Flawed Decidualization in Recurrent Implantation Failure by Modulating HOXC8

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2020 Aug 11

PMID 32772270

Citations 9

Authors

Qian Zhang

Tianxiang Ni

Yujie Dang

Lingling Ding

Jingjing Jiang

Jing Li

Mingdi Xia

Na Yu

Jinlong Ma

Junhao Yan

Zi-Jiang Chen

Affiliations

Soon will be listed here.

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.

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References

Noyes R, Hertig A, Rock J . Reprint of: Dating the Endometrial Biopsy. Fertil Steril. 2019; 112(4 Suppl1):e93-e115. DOI: 10.1016/j.fertnstert.2019.08.079. View

Vinketova K, Mourdjeva M, Oreshkova T . Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity. J Pregnancy. 2016; 2016:8689436. PMC: 4864559. DOI: 10.1155/2016/8689436. View

Kang Y, Lees M, Matthews L, Kimber S, Forbes K, Aplin J . MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R. J Cell Sci. 2015; 128(4):804-14. DOI: 10.1242/jcs.164004. View

Engels B, Hutvagner G . Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene. 2006; 25(46):6163-9. DOI: 10.1038/sj.onc.1209909. View

Liu H, Zhang M, Xu S, Zhang J, Zou J, Yang C . HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFβ1 in non-small cell lung cancer. Oncogenesis. 2018; 7(2):1. PMC: 5833702. DOI: 10.1038/s41389-017-0016-4. View

Berkhout R, Lambalk C, Repping S, Hamer G, Mastenbroek S . Premature expression of the decidualization marker prolactin is associated with repeated implantation failure. Gynecol Endocrinol. 2019; 36(4):360-364. DOI: 10.1080/09513590.2019.1650344. View

Choi Y, Kim H, Lim E, Park M, Yoon J, Kim Y . Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF). PLoS One. 2016; 11(6):e0157696. PMC: 4909214. DOI: 10.1371/journal.pone.0157696. View

Coutifaris C, Myers E, Guzick D, Diamond M, Carson S, Legro R . Reprint of: Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril. 2019; 112(4 Suppl1):e116-e124. DOI: 10.1016/j.fertnstert.2019.08.080. View

Wang X, Liang Z, Xu X, Li J, Zhu Y, Meng S . miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer. Cell Death Dis. 2016; 7(12):e2503. PMC: 5261009. DOI: 10.1038/cddis.2016.373. View

10.

Cha J, Sun X, Dey S . Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012; 18(12):1754-67. PMC: 6322836. DOI: 10.1038/nm.3012. View

11.

Gellersen B, Brosens J . Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev. 2014; 35(6):851-905. DOI: 10.1210/er.2014-1045. View

12.

Sha A, Liu J, Jiang X, Ren J, Ma C, Lei W . Genome-wide identification of micro-ribonucleic acids associated with human endometrial receptivity in natural and stimulated cycles by deep sequencing. Fertil Steril. 2011; 96(1):150-155.e5. DOI: 10.1016/j.fertnstert.2011.04.072. View

13.

Niklaus A, Aubuchon M, Zapantis G, Li P, Qian H, Isaac B . Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women. Hum Reprod. 2007; 22(6):1778-88. DOI: 10.1093/humrep/dem032. View

14.

Ochoa-Bernal M, Fazleabas A . Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates. Int J Mol Sci. 2020; 21(6). PMC: 7139778. DOI: 10.3390/ijms21061973. View

15.

Cao C, Sun J, Zhang D, Guo X, Xie L, Li X . The long intergenic noncoding RNA UFC1, a target of MicroRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of β-catenin in HCC cells. Gastroenterology. 2014; 148(2):415-26.e18. DOI: 10.1053/j.gastro.2014.10.012. View

16.

Chill H, Dior U, Kogan L, Revel A . microRNAs and Endometrial Pathophysiology. Adv Exp Med Biol. 2015; 887:143-55. DOI: 10.1007/978-3-319-22380-3_8. View

17.

Estella C, Herrer I, Moreno-Moya J, Quinonero A, Martinez S, Pellicer A . miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro. PLoS One. 2012; 7(7):e41080. PMC: 3401238. DOI: 10.1371/journal.pone.0041080. View

18.

Reinhart B, Slack F, Basson M, Pasquinelli A, Bettinger J, Rougvie A . The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403(6772):901-6. DOI: 10.1038/35002607. View

19.

Gellersen B, Brosens J . Cyclic AMP and progesterone receptor cross-talk in human endometrium: a decidualizing affair. J Endocrinol. 2003; 178(3):357-72. DOI: 10.1677/joe.0.1780357. View

20.

Seki N, Hata A . Noncoding RNAs: a new fine-tuner is a key player of human pathogenesis. J Hum Genet. 2017; 62(1):1. DOI: 10.1038/jhg.2016.140. View