{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:14:04Z","timestamp":1791285244190,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Priority Research Centers Program through the National Research Foundation of Korea (NRF)","award":["NRF-2017R1A6A1A03015713"],"award-info":[{"award-number":["NRF-2017R1A6A1A03015713"]}]},{"DOI":"10.13039\/501100003725","name":"the Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2017R1A6A1A03015713"],"award-info":[{"award-number":["NRF-2017R1A6A1A03015713"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-\u03ba\u0392 (NF-\u03ba\u0392)\/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-\u03ba\u0392\/ZEB1\/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.<\/jats:p>","DOI":"10.3390\/ijms232012303","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"12303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The miR-182-5p\/NDRG1 Axis Controls Endometrial Receptivity through the NF-\u03baB\/ZEB1\/E-Cadherin Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Seong-Lan","family":"Yu","sequence":"first","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Kang","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Un","family":"Jeong","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"},{"name":"Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"},{"name":"Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5432-548X","authenticated-orcid":false,"given":"Ae Ra","family":"Han","sequence":"additional","affiliation":[{"name":"I-Dream Clinic, Department of Obstetrics and Gynecology, Mizmedi Hospital, Seoul 07639, Korea"},{"name":"Daegu cha Fertility Center, CHA University, Daegu 42469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-7940","authenticated-orcid":false,"given":"Jaeku","family":"Kang","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"},{"name":"Department of Pharmacology, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-4495","authenticated-orcid":false,"given":"Seok-Rae","family":"Park","sequence":"additional","affiliation":[{"name":"Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea"},{"name":"Department of Microbiology, College of Medicine, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1471-0528.1997.tb11490.x","article-title":"Adhesion molecules in reproduction","volume":"104","author":"Klentzeris","year":"1997","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.1016\/j.febslet.2006.09.014","article-title":"Profiling of E-cadherin, \u03b2-catenin and Ca2+ in embryo-uterine interactions at implantation","volume":"580","author":"Jha","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target Recognition and Regulatory Functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","article-title":"Metazoan MicroRNAs","volume":"173","author":"Bartel","year":"2018","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/biolre\/ioz014","article-title":"MicroRNAs in endometriosis: Biological function and emerging biomarker candidates\u2020","volume":"101","author":"Bjorkman","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/jcp.27291","article-title":"Roles of microRNAs in preeclampsia","volume":"234","author":"Lv","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12958-017-0309-7","article-title":"Role of microRNAs in embryo implantation","volume":"15","author":"Liang","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1093\/nar\/gkv703","article-title":"The microRNA-183 cluster: The family that plays together stays together","volume":"43","author":"Dambal","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/abbs\/gmw105","article-title":"MicroRNA-182 promotes pancreatic cancer cell proliferation and migration by targeting \u03b2-TrCP2","volume":"48","author":"Wang","year":"2016","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116689","DOI":"10.1016\/j.jns.2020.116689","article-title":"MiR-182 promotes glioma progression by targeting FBXW7","volume":"411","author":"Liu","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7074343","DOI":"10.1155\/2021\/7074343","article-title":"miR-182-5p Serves as an Oncogene in Lung Adenocarcinoma through Binding to STARD13","volume":"2021","author":"Wu","year":"2021","journal-title":"Comput. Math. Methods Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7120","DOI":"10.7150\/jca.60419","article-title":"MiR-182-5p promotes the Metastasis and Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Targeting EPAS1","volume":"12","author":"Yang","year":"2021","journal-title":"J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.3892\/ol.2017.6778","article-title":"MicroRNA-182 promotes proliferation and metastasis by targeting FOXF2 in triple-negative breast cancer","volume":"14","author":"Zhang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/jb\/mvaa014","article-title":"MicroRNA-191 regulates endometrial cancer cell growth via TET1-mediated epigenetic modulation of APC","volume":"168","author":"Yang","year":"2020","journal-title":"J. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"660","DOI":"10.3892\/etm.2021.10092","article-title":"Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid-secretory phases","volume":"21","author":"Yu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/molehr\/gag084","article-title":"Large scale validation of human N-myc Downstream-Regulated Gene (NDRG)-1 expression in endometrium during the menstrual cycle","volume":"9","author":"Malette","year":"2003","journal-title":"Mol. Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10077","DOI":"10.1038\/s41598-017-10098-3","article-title":"Meta-signature of human endometrial receptivity: A meta-analysis and validation study of transcriptomic biomarkers","volume":"7","author":"Koel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.fertnstert.2012.01.116","article-title":"A high-throughput in vitro model of human embryo attachment","volume":"97","author":"Ho","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.bbrc.2006.02.189","article-title":"Effects of E-cadherin on mouse embryo implantation and expression of matrix metalloproteinase-2 and -9","volume":"343","author":"Liu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1210\/en.2008-1142","article-title":"Epigenetic Regulation of E-Cadherin Controls Endometrial Receptivity","volume":"150","author":"Rahnama","year":"2008","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/carcin\/bgy178","article-title":"The metastasis suppressor, NDRG1, attenuates oncogenic TGF-\u03b2 and NF-\u03baB signaling to enhance membrane E-cadherin expression in pancreatic cancer cells","volume":"40","author":"Menezes","year":"2019","journal-title":"Carcinogenesis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1093\/carcin\/bgt163","article-title":"Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors","volume":"34","author":"Sun","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/sj.onc.1209808","article-title":"NF-\u03baB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2","volume":"26","author":"Chua","year":"2006","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.rbmo.2013.05.018","article-title":"Implantation in assisted reproduction: A look at endometrial receptivity","volume":"27","author":"Fatemi","year":"2013","journal-title":"Reprod. Biomed. Online"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1095\/biolreprod.109.081059","article-title":"Genomic Profiling of MicroRNAs and Messenger RNAs Reveals Hormonal Regulation in MicroRNA Expression in Human Endometrium1","volume":"82","author":"Kuokkanen","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.fertnstert.2011.04.072","article-title":"Genome-wide identification of micro-ribonucleic acids associated with human endometrial receptivity in natural and stimulated cycles by deep sequencing","volume":"96","author":"Sha","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/1933719112453507","article-title":"MicroRNAs miR-30b, miR-30d, and miR-494 Regulate Human Endometrial Receptivity","volume":"20","author":"Esteban","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1093\/molehr\/gau010","article-title":"The transcriptomic and proteomic effects of ectopic overexpression of miR-30d in human endometrial epithelial cells","volume":"20","author":"Vilella","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4103\/0366-6999.200550","article-title":"Endometrial MicroRNA Signature during the Window of Implantation Changed in Patients with Repeated Implantation Failure","volume":"130","author":"Shi","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1038\/cdd.2017.136","article-title":"MicroRNA-200c impairs uterine receptivity formation by targeting FUT4 and \u03b11,3-fucosylation","volume":"24","author":"Zheng","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/1933719118799199","article-title":"Endometrial miR-543 Is Downregulated During the Implantation Window in Women With Endometriosis-Related Infertility","volume":"26","author":"Yang","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1530\/JME-19-0184","article-title":"miR-183-5p regulates uterine receptivity and enhances embryo implantation","volume":"64","author":"Akbar","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"gaab039","DOI":"10.1093\/molehr\/gaab039","article-title":"miRNA-149 targets PARP-2 in endometrial epithelial and stromal cells to regulate the trophoblast attachment process","volume":"27","author":"Soni","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.112.098871","article-title":"Cdh1 Is Essential for Endometrial Differentiation, Gland Development, and Adult Function in the Mouse Uterus1","volume":"86","author":"Reardon","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1016\/j.fertnstert.2010.04.055","article-title":"Expression of E- and N-cadherin and CD44 in endometrium and hydrosalpinges from infertile women","volume":"94","author":"Poncelet","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1210\/jc.2009-2713","article-title":"Impaired Down-Regulation of E-Cadherin and \u03b2-Catenin Protein Expression in Endometrial Epithelial Cells in the Mid-Secretory Endometrium of Infertile Patients with Endometriosis","volume":"95","author":"Matsuzaki","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Souza, M.F., C\u00f3lus, I.M.S., Fonseca, A.S., Antunes, V.C., Kumar, D., and Cavalli, L.R. (2022). MiR-182-5p Modulates Prostate Cancer Aggressive Phenotypes by Targeting EMT Associated Pathways. Biomolecules, 12.","DOI":"10.3390\/biom12020187"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/mrd.23238","article-title":"Decreased NDRG1 expression is associated with pregnancy loss in mice and attenuates the in vitro decidualization of endometrial stromal cells","volume":"86","author":"Meng","year":"2019","journal-title":"Mol. Reprod. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1038\/onc.2017.74","article-title":"The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells","volume":"36","author":"Mi","year":"2017","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/j.bbadis.2015.06.009","article-title":"NDRG1 attenuates epithelial\u2013mesenchymal transition of nasopharyngeal cancer cells via blocking Smad2 signaling","volume":"1852","author":"Hu","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4983","DOI":"10.1158\/0008-5472.CAN-08-4882","article-title":"N-myc Downstream Regulated Gene 1\/Cap43 Suppresses Tumor Growth and Angiogenesis of Pancreatic Cancer through Attenuation of Inhibitor of \u03baB Kinase \u03b2 Expression","volume":"69","author":"Hosoi","year":"2009","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/jso.24348","article-title":"Knockdown of NDRG1 promote epithelial-mesenchymal transition of colorectal cancer via NF-\u03baB signaling","volume":"114","author":"Ma","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1016\/j.fertnstert.2019.08.079","article-title":"Reprint of: Dating the Endometrial Biopsy","volume":"112","author":"Noyes","year":"2019","journal-title":"Fertil. Steril."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:54:13Z","timestamp":1760144053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012303"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012303","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}