miR-23a-3p increases endometrial receptivity via CUL3 during embryo implantation

in Journal of Molecular Endocrinology
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  • 1 Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 2 Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Correspondence should be addressed to L Hu: acceptzzu@126.com
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A receptive endometrium is required in a successful embryo implantation. The ubiquitination-induced β-catenin degradation is related to the implantation failure.This study aimed to elucidate whether miR-23a-3p regulates endometrial receptivity via the modulation of β-catenin ubiquitination.The expressions of miR-23a-3p and CUL3 were detected in endometrial epithelial cells (EECs) isolated from pregnant mice and in hormone-induced EEC-like Ishikawa cells. The ubiquitination experiment was performed to explore the effect of CUL3 and miR-23a-3p on β-catenin ubiquitination level. The trophoblast attachment was detected by co-culturing JAR (choriocarcinoma cell line) spheroids with Ishikawa cell monolayers. miR-23a-3p was upregulated while CUL3 was downregulated in EECs at day 4 after pregnancy compared with day 1, as well as in hormone-induced Ishikawa cells. miR-23a-3p positively regulated the protein level of β-catenin without affecting the mRNA level. The ubiquitination and degradation of β-catenin was suppressed by miR-23a-3p, while it was promoted by CUL3. Immunoprecipitation confirmed the binding between CUL3 and β-catenin. Luciferase reporter assay confirmed the target relationship between miR-23a-3p and CUL3. The ubiquitination of β-catenin was modulated by the miR-23a-3p/CUL3 pathway. The overexpression of miR-23a-3p promoted JAR spheroid attachments in Ishikawa cells. miR-23a-3p is beneficial for the endometrial receptivity and embryo implantation, whose mechanism is partly through the modulation of CUL3/β-catenin.

 

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  • Angers S, Thorpe CJ, Biechele TL, Goldenberg SJ, Zheng N, MacCoss MJ & Moon RT 2006 The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting dishevelled for degradation. Nature Cell Biology 8 348357. (https://doi.org/10.1038/ncb1381)

    • Search Google Scholar
    • Export Citation
  • Beermann J, Piccoli MT, Viereck J & Thum T 2016 Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiological Reviews 96 12971325. ( https://doi.org/10.1152/physrev.00041.2015)

    • Search Google Scholar
    • Export Citation
  • Berneau SC, Ruane PT, Brison DR, Kimber SJ, Westwood M & Aplin JD 2019 Characterisation of osteopontin in an in vitro model of embryo implantation. Cells 8 432. (https://doi.org/10.3390/cells8050432)

    • Search Google Scholar
    • Export Citation
  • Cagil N, Ugurlu N, Cakmak HB, Ilker Kocamis S, Turak D & Simsek S 2011 Photorefractive keratectomy in treatment of refractive amblyopia in the adult population. Journal of Cataract and Refractive Surgery 37 21672174. (https://doi.org/10.1016/j.jcrs.2011.06.026)

    • Search Google Scholar
    • Export Citation
  • Chakrabarty A, Tranguch S, Daikoku T, Jensen K, Furneaux H & Dey SK 2007 MicroRNA regulation of cyclooxygenase-2 during embryo implantation. PNAS 104 1514415149. (https://doi.org/10.1073/pnas.0705917104)

    • Search Google Scholar
    • Export Citation
  • Diedrich K, Fauser BC, Devroey P, Griesinger G & Evian Annual Reproduction (EVAR) Workshop Group 2007 The role of the endometrium and embryo in human implantation. Human Reproduction Update 13 365377. (https://doi.org/10.1093/humupd/dmm011)

    • Search Google Scholar
    • Export Citation
  • Garrido-Gomez T, Dominguez F, Quinonero A, Estella C, Vilella F, Pellicer A & Simon C 2012 Annexin A2 is critical for embryo adhesiveness to the human endometrium by RhoA activation through F-actin regulation. FASEB Journal 26 37153727. (https://doi.org/10.1096/fj.12-204008)

    • Search Google Scholar
    • Export Citation
  • Godfrey TC, Wildman BJ, Beloti MM, Kemper AG, Ferraz EP, Roy B, Rehan M, Afreen LH, Kim E, Lengner CJ, 2018 The microRNA-23a cluster regulates the developmental HoxA cluster function during osteoblast differentiation. Journal of Biological Chemistry 293 1764617660. (https://doi.org/10.1074/jbc.RA118.003052)

    • Search Google Scholar
    • Export Citation
  • Haouzi D, Mahmoud K, Fourar M, Bendhaou K, Dechaud H, De Vos J, Reme T, Dewailly D & Hamamah S 2009 Identification of new biomarkers of human endometrial receptivity in the natural cycle. Human Reproduction 24 198205. (https://doi.org/10.1093/humrep/den360)

    • Search Google Scholar
    • Export Citation
  • Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O, Mavrogianis P, Ferrer K & Kruessel J, 2007 Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biology of Reproduction 76 102117. (https://doi.org/10.1095/biolreprod.106.054791)

    • Search Google Scholar
    • Export Citation
  • Hu SJ, Ren G, Liu JL, Zhao ZA, Yu YS, Su RW, Ma XH, Ni H, Lei W & Yang ZM 2008 MicroRNA expression and regulation in mouse uterus during embryo implantation. Journal of Biological Chemistry 283 2347323484. (https://doi.org/10.1074/jbc.M800406200)

    • Search Google Scholar
    • Export Citation
  • Li D, Jiang W, Jiang Y, Wang S, Fang J, Zhu L, Zhu Y, Yan G, Sun H & Chen L, 2019 Preliminary functional inquiry of lncRNA ENST00000433673 in embryo implantation using bioinformatics analysis. Systems Biology in Reproductive Medicine 65 164173. (https://doi.org/10.1080/19396368.2018.1563844)

    • Search Google Scholar
    • Export Citation
  • Li HWR, Li YX, Li TT, Fan H, Ng EH, Yeung WS, Ho PC & Lee KF 2017 Effect of ulipristal acetate and mifepristone at emergency contraception dose on the embryo-endometrial attachment using an in vitro human trophoblastic spheroid and endometrial cell co-culture model. Human Reproduction 32 24142422. (https://doi.org/10.1093/humrep/dex328)

    • Search Google Scholar
    • Export Citation
  • Lim HJ & Wang H 2010 Uterine disorders and pregnancy complications: insights from mouse models. Journal of Clinical Investigation 120 10041015. (https://doi.org/10.1172/JCI41210)

    • Search Google Scholar
    • Export Citation
  • Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X & He X 2002 Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108 837847. (https://doi.org/10.1016/s0092-8674(02)00685-2)

    • Search Google Scholar
    • Export Citation
  • Liu Y, Kodithuwakku SP, Ng PY, Chai J, Ng EH, Yeung WS, Ho PC & Lee KF 2010 Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: an in vitro co-culture study. Human Reproduction 25 479490. (https://doi.org/10.1093/humrep/dep429)

    • Search Google Scholar
    • Export Citation
  • Mohamed OA, Dufort D & Clarke HJ 2004 Expression and estradiol regulation of Wnt genes in the mouse blastocyst identify a candidate pathway for embryo-maternal signaling at implantation. Biology of Reproduction 71 417424. (https://doi.org/10.1095/biolreprod.103.025692)

    • Search Google Scholar
    • Export Citation
  • Pan JL, Yuan DZ, Zhao YB, Nie L, Lei Y, Liu M, Long Y, Zhang JH, Blok LJ, Burger CW, 2017 Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells. Acta Physiologica 219 683692. (https://doi.org/10.1111/apha.12762)

    • Search Google Scholar
    • Export Citation
  • Petroski MD & Deshaies RJ 2005 Function and regulation of cullin-RING ubiquitin ligases. Nature Reviews: Molecular Cell Biology 6 920. (https://doi.org/10.1038/nrm1547)

    • Search Google Scholar
    • Export Citation
  • Schmitz C, Yu L, Bocca S, Anderson S, Cunha-Filho JS, Rhavi BS & Oehninger S 2014 Role for the endometrial epithelial protein MFG-E8 and its receptor integrin alphavbeta3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines. Fertility and Sterility 101 874882. (https://doi.org/10.1016/j.fertnstert.2013.12.015)

    • Search Google Scholar
    • Export Citation
  • Sonderegger S, Pollheimer J & Knofler M 2010 Wnt signalling in implantation, decidualisation and placental differentiation – review. Placenta 31 839847. (https://doi.org/10.1016/j.placenta.2010.07.011)

    • Search Google Scholar
    • Export Citation
  • Takamura M, Zhou W, Rombauts L & Dimitriadis E 2019 The long non-coding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility. Biology of Reproduction 102 53–62. (https://doi.org/10.1093/biolre/ioz173)

    • Search Google Scholar
    • Export Citation
  • Taylor HS 2000 The role of HOX genes in human implantation. Human Reproduction Update 6 7579. (https://doi.org/10.1093/humupd/6.1.75)

  • Wang J, Ke L, Jiang X-l & Zhang C 2018 A review of microRNAs related to the occurrence, diagnosis, and prognosis of non-small cell lung cancer. Clinical Surgery Research Communications 2 18. (https://doi.org/10.31491/CSRC.2018.9.017)

    • Search Google Scholar
    • Export Citation
  • Yang Q, Gu WW, Gu Y, Yan NN, Mao YY, Zhen XX, Wang JM, Yang J, Shi HJ & Zhang X, 2018 Association of the peripheral blood levels of circulating microRNAs with both recurrent miscarriage and the outcomes of embryo transfer in an in vitro fertilization process. Journal of Translational Medicine 16 186. (https://doi.org/10.1186/s12967-018-1556-x)

    • Search Google Scholar
    • Export Citation
  • Zhang Q, Yu S, Huang X, Tan Y, Zhu C, Wang YL, Wang H, Lin HY, Fu J & Wang H 2015 New insights into the function of cullin 3 in trophoblast invasion and migration. Reproduction 150 139149. (https://doi.org/10.1530/REP-15-0126)

    • Search Google Scholar
    • Export Citation
  • Zhao C, Wang S, Zhao Y, Du F, Wang W, Lv P & Qi L 2019 Long noncoding RNA NEAT1 modulates cell proliferation and apoptosis by regulating miR-23a-3p/SMC1A in acute myeloid leukemia. Journal of Cellular Physiology 234 61616172. (https://doi.org/10.1002/jcp.27393)

    • Search Google Scholar
    • Export Citation
  • Zheng N & Shabek N 2017 Ubiquitin ligases: structure, function, and regulation. Annual Review of Biochemistry 86 129157. (https://doi.org/10.1146/annurev-biochem-060815-014922)

    • Search Google Scholar
    • Export Citation
  • Zheng Q, Dai K, Cui X, Yu M, Yang X, Yan B, Liu S & Yan Q 2016 Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia. Biomedicine and Pharmacotherapy 80 102108. (https://doi.org/10.1016/j.biopha.2016.03.005)

    • Search Google Scholar
    • Export Citation
  • Zhu LH, Sun LH, Hu YL, Jiang Y, Liu HY, Shen XY, Jin XY, Zhen X, Sun HX & Yan GJ 2013 PCAF impairs endometrial receptivity and embryo implantation by down-regulating beta3-integrin expression via HOXA10 acetylation. Journal of Clinical Endocrinology and Metabolism 98 44174428. (https://doi.org/10.1210/jc.2013-1429)

    • Search Google Scholar
    • Export Citation