{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:29:23Z","timestamp":1787804963600,"version":"build-2784847793"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601281"],"award-info":[{"award-number":["81601281"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771543"],"award-info":[{"award-number":["81771543"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042018kf0094"],"award-info":[{"award-number":["2042018kf0094"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Decidualization of human endometrial stromal cells (HESCs) is a vital step for successful pregnancy. However, the process by which micro-RNAs (miRNAs) regulate decidualization remains elusive. Our current study was designed to identify the mechanism of miRNA miR-542-3p and its potential targets in regulating decidualization. The results showed that miR-542-3p was down-regulated in HESCs. Luciferase assay confirmed that integrin-linked kinase (ILK) is a direct target of miR-542-3p. Overexpression of miR-542-3p resulted in decreased ILK and downstream transforming growth factor \u03b21 (TGF-\u03b21) and SMAD family member 2 (SMAD2) expression. Additional expression of ILK attenuates the miR542-3p-induced down-regulation of TGF-\u03b21 and SMAD2, changes properties such as suppression of proliferation and invasion, and induction of apoptosis, thereby affecting the differentiation of HESCs. Moreover, miR-542-3p overexpression caused down-regulation of the angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), and the supernatant of HESCs overexpressing miR-542-3p inhibited the formation of tubular structures in human umbilical vein endothelial cells (HUVECs), suggesting that miR-542-3p inhibits angiogenesis of HUVECs. Furthermore, in our mouse model, following injection of miR-542-3p mimic into the endometrium of mice at pregnancy day 8 (D8), we found decreased miR-542-3p expression and loss of embryo implantation sites. In conclusion, miR-542-3p can affect the process of endometrial decidualization by down-regulating ILK. The present study adds further understanding of the process and regulation of decidualization.<\/jats:p>","DOI":"10.1038\/s41598-021-85295-2","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T10:03:41Z","timestamp":1617098621000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Micro-RNA miR-542-3p suppresses decidualization by targeting ILK pathways in human endometrial stromal cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Xinlan","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"85295_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1111\/eci.12417","volume":"45","author":"A Makrigiannakis","year":"2015","unstructured":"Makrigiannakis, A. et al. Repeated implantation failure: A new potential treatment option. Eur. J. Clin. Invest. 45, 380\u2013384 (2015).","journal-title":"Eur. J. Clin. Invest."},{"key":"85295_CR2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1055\/s-2007-991042","volume":"25","author":"B Gellersen","year":"2007","unstructured":"Gellersen, B., Brosens, I. A. & Brosens, J. J. Decidualization of the human endometrium: Mechanisms, functions, and clinical perspectives. Semin. Reprod. Med. 25, 445\u2013453 (2007).","journal-title":"Semin. Reprod. Med."},{"key":"85295_CR3","first-page":"e225249","volume":"14","author":"D Oliveira","year":"2019","unstructured":"Oliveira, D. et al. Diagnostic plasma mirna-profiles for ovarian cancer in patients with pelvic mass. PLoS ONE 14, e225249 (2019).","journal-title":"PLoS ONE"},{"key":"85295_CR4","doi-asserted-by":"publisher","first-page":"5499","DOI":"10.3390\/ijms20215499","volume":"20","author":"R Spear","year":"2019","unstructured":"Spear, R. et al. Let-7F: A new potential circulating biomarker identified by mirna profiling of cells isolated from human abdominal aortic aneurysm. Int. J. Mol. Sci. 20, 5499 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"85295_CR5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/humrep\/dex347","volume":"33","author":"L Hong","year":"2018","unstructured":"Hong, L. et al. Down-regulation of Mir-378a-3p induces decidual cell apoptosis: A possible mechanism for early pregnancy loss. Hum. Reprod. 33, 11\u201322 (2018).","journal-title":"Hum. Reprod."},{"key":"85295_CR6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ajog.2019.02.047","volume":"221","author":"N Balaguer","year":"2019","unstructured":"Balaguer, N. et al. Microrna-30D deficiency during preconception affects endometrial receptivity by decreasing implantation rates and impairing fetal growth. Am. J. Obstet. Gynecol. 221, 41\u201346 (2019).","journal-title":"Am. J. Obstet. Gynecol."},{"key":"85295_CR7","doi-asserted-by":"publisher","first-page":"E557","DOI":"10.1152\/ajpendo.00245.2018","volume":"316","author":"L Nie","year":"2019","unstructured":"Nie, L. et al. Progesterone-induced mir-152 interferes with embryonic implantation by downregulating Glut3 in endometrial epithelium. Am. J. Physiol. Endocrinol. Metab. 316, E557\u2013E567 (2019).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"85295_CR8","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1071\/RD17095","volume":"30","author":"A Winship","year":"2018","unstructured":"Winship, A. et al. Mouse double minute homologue 2 (Mdm2) downregulation by Mir-661 impairs human endometrial epithelial cell adhesive capacity. Reprod. Fertil. Dev. 30, 477\u2013486 (2018).","journal-title":"Reprod. Fertil. Dev."},{"key":"85295_CR9","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1038\/cdd.2017.136","volume":"24","author":"Q Zheng","year":"2017","unstructured":"Zheng, Q. et al. Microrna-200C impairs uterine receptivity formation by targeting Fut4 and Alpha 1,3-fucosylation. Cell Death Differ. 24, 2161\u20132172 (2017).","journal-title":"Cell Death Differ."},{"key":"85295_CR10","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.3892\/ijmm.2016.2505","volume":"37","author":"HC Long","year":"2016","unstructured":"Long, H. C. et al. Mir-542-3P inhibits the growth and invasion of colorectal cancer cells through targeted regulation of cortactin. Int. J. Mol. Med. 37, 1112\u20131118 (2016).","journal-title":"Int. J. Mol. Med."},{"key":"85295_CR11","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3233\/CBM-170255","volume":"21","author":"Q Li","year":"2018","unstructured":"Li, Q., Song, S., Ni, G., Li, Y. & Wang, X. Serum Mir-542-3P as a prognostic biomarker in osteosarcoma. Cancer Biomark. 21, 521\u2013526 (2018).","journal-title":"Cancer Biomark."},{"key":"85295_CR12","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.biopha.2018.01.131","volume":"99","author":"XP Wang","year":"2018","unstructured":"Wang, X. P. et al. Microrna-542-3P functions as a tumor suppressor via directly targeting survivin in hepatocellular carcinoma. Biomed. Pharmacother. 99, 817\u2013824 (2018).","journal-title":"Biomed. Pharmacother."},{"key":"85295_CR13","doi-asserted-by":"publisher","first-page":"e1050","DOI":"10.1038\/cddis.2014.4","volume":"5","author":"J Kureel","year":"2014","unstructured":"Kureel, J. et al. Mir-542-3P suppresses osteoblast cell proliferation and differentiation, targets Bmp-7 signaling and inhibits bone formation. Cell Death Dis. 5, e1050 (2014).","journal-title":"Cell Death Dis."},{"key":"85295_CR14","doi-asserted-by":"publisher","first-page":"70761","DOI":"10.18632\/oncotarget.19986","volume":"8","author":"B Qiao","year":"2017","unstructured":"Qiao, B., Cai, J. H., King-Yin, L. A. & He, B. X. Microrna-542-3P inhibits oral squamous cell carcinoma progression by inhibiting Ilk\/Tgf-Beta1\/Smad2\/3 signaling. Oncotarget. 8, 70761\u201370776 (2017).","journal-title":"Oncotarget."},{"key":"85295_CR15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.canlet.2018.01.065","volume":"420","author":"H Lyu","year":"2018","unstructured":"Lyu, H. et al. Survivin-targeting Mir-542-3P overcomes Her3 signaling-induced chemoresistance and enhances the antitumor activity of paclitaxel against Her2-overexpressing breast cancer. Cancer Lett. 420, 97\u2013108 (2018).","journal-title":"Cancer Lett."},{"key":"85295_CR16","first-page":"3545","volume":"38","author":"C Yang","year":"2017","unstructured":"Yang, C., Wang, M. H., Zhou, J. D. & Chi, Q. Upregulation of Mir-542-3P inhibits the growth and invasion of human colon cancer cells through Pi3K\/Akt\/survivin signaling. Oncol. Rep. 38, 3545\u20133553 (2017).","journal-title":"Oncol. Rep."},{"key":"85295_CR17","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.canlet.2015.07.036","volume":"368","author":"T He","year":"2015","unstructured":"He, T. et al. Tumor cell-secreted angiogenin induces angiogenic activity of endothelial cells by suppressing Mir-542-3P. Cancer Lett. 368, 115\u2013125 (2015).","journal-title":"Cancer Lett."},{"key":"85295_CR18","doi-asserted-by":"publisher","first-page":"7675","DOI":"10.12659\/MSM.917013","volume":"25","author":"Z Lu","year":"2019","unstructured":"Lu, Z. et al. Resveratrol induces endothelial progenitor cells angiogenesis via Mir-542-3P by targeting angiopoietin-2 and involves in recanalization of venous thrombosis. Med. Sci. Monit. 25, 7675\u20137683 (2019).","journal-title":"Med. Sci. Monit."},{"key":"85295_CR19","doi-asserted-by":"publisher","first-page":"40001","DOI":"10.1038\/srep40001","volume":"7","author":"H Tochigi","year":"2017","unstructured":"Tochigi, H. et al. Loss of Mir-542-3P enhances Igfbp-1 expression in decidualizing human endometrial stromal cells. Sci. Rep. 7, 40001 (2017).","journal-title":"Sci. Rep."},{"key":"85295_CR20","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1210\/en.2003-1606","volume":"145","author":"G Krikun","year":"2004","unstructured":"Krikun, G. et al. A novel immortalized human endometrial stromal cell line with normal progestational response. Endocrinology 145, 2291\u20132296 (2004).","journal-title":"Endocrinology"},{"key":"85295_CR21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1177\/1933719117711258","volume":"25","author":"XL Qu","year":"2018","unstructured":"Qu, X. L., Ming-Zhang, Y. F., Whang, H. & Zhang, Y. Z. Effect of 2,3\u2019,4,4\u2019,5-pentachlorobiphenyl exposure on endometrial receptivity and the methylation of Hoxa10. Reprod. Sci. 25, 256\u2013268 (2018).","journal-title":"Reprod. Sci."},{"key":"85295_CR22","first-page":"289","volume":"23","author":"M Li","year":"2019","unstructured":"Li, M., Zhou, H., Di, J., Yang, M. & Jia, F. Ilk participates in renal interstitial fibrosis by altering the phenotype of renal tubular epithelial cells via Tgf-Beta1\/Smad pathway. Eur. Rev. Med. Pharmacol. Sci. 23, 289\u2013296 (2019).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"85295_CR23","first-page":"3015","volume":"41","author":"FH Qi","year":"2018","unstructured":"Qi, F. H., Cai, P. P., Liu, X. & Si, G. M. Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via Tgf-Beta1-Smad-Ilk pathway in unilateral ureteral obstruction rats. Int. J. Mol. Med. 41, 3015\u20133023 (2018).","journal-title":"Int. J. Mol. Med."},{"key":"85295_CR24","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/path.4324","volume":"232","author":"T He","year":"2014","unstructured":"He, T. et al. Microrna-542-3P inhibits tumour angiogenesis by targeting angiopoietin-2. J. Pathol. 232, 499\u2013508 (2014).","journal-title":"J. Pathol."},{"key":"85295_CR25","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1158\/1538-7445.AM2019-186","volume":"9","author":"CC Zheng","year":"2019","unstructured":"Zheng, C. C. et al. Significance of integrin-linked kinase (Ilk) in tumorigenesis and its potential implication as a biomarker and therapeutic target for human cancer. Am. J. Cancer Res. 9, 186\u2013197 (2019).","journal-title":"Am. J. Cancer Res."},{"key":"85295_CR26","first-page":"1101","volume":"16","author":"W Zhao","year":"2018","unstructured":"Zhao, W. et al. Ilk promotes angiogenic activity of mesenchymal stem cells in multiple myeloma. Oncol. Lett. 16, 1101\u20131106 (2018).","journal-title":"Oncol. Lett."},{"key":"85295_CR27","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s40246-019-0245-z","volume":"13","author":"H Liu","year":"2019","unstructured":"Liu, H., Wang, H., Yang, S. & Qian, D. Downregulation of Mir-542-3P promotes osteogenic transition of vascular smooth muscle cells in the aging rat by targeting Bmp7. Hum Genom. 13, 67 (2019).","journal-title":"Hum Genom."},{"key":"85295_CR28","unstructured":"Li, Q., Liu, W., Li, S. & Zhang, S. Long non-coding rna casc15 favors tumorigenesis and development of ovarian cancer via sponging Mir-542-3P. Panminerva Med. (2019)."},{"key":"85295_CR29","first-page":"159","volume":"7","author":"L Yuan","year":"2017","unstructured":"Yuan, L. et al. Mir-542-3P inhibits colorectal cancer cell proliferation, migration and invasion by targeting Otub1. Am. J. Cancer Res. 7, 159\u2013172 (2017).","journal-title":"Am. J. Cancer Res."},{"key":"85295_CR30","first-page":"108","volume":"21","author":"HX Wu","year":"2017","unstructured":"Wu, H. X., Wang, G. M., Lu, X. & Zhang, L. Mir-542-3P targets sphingosine-1-phosphate receptor 1 and regulates cell proliferation and invasion of breast cancer cells. Eur. Rev. Med.. Pharmacol. Sci. 21, 108\u2013114 (2017).","journal-title":"Eur. Rev. Med.. Pharmacol. Sci."},{"key":"85295_CR31","doi-asserted-by":"publisher","first-page":"e41080","DOI":"10.1371\/journal.pone.0041080","volume":"7","author":"C Estella","year":"2012","unstructured":"Estella, C. et al. Mirna signature and dicer requirement during human endometrial stromal decidualization in vitro. PLoS ONE 7, e41080 (2012).","journal-title":"PLoS ONE"},{"key":"85295_CR32","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/rmb2.12028","volume":"16","author":"S Sultana","year":"2017","unstructured":"Sultana, S. et al. Overexpression of microrna-542-3P attenuates the differentiating capacity of endometriotic stromal cells. Reprod. Med. Biol. 16, 170\u2013178 (2017).","journal-title":"Reprod. Med. Biol."},{"key":"85295_CR33","doi-asserted-by":"publisher","first-page":"9287","DOI":"10.3892\/mmr.2017.7820","volume":"16","author":"L Liu","year":"2017","unstructured":"Liu, L. et al. Hmga1 participates in Mhcc97H cell proliferation and invasion through the Ilk\/Akt\/Gsk3Beta signaling pathway. Mol. Med. Rep. 16, 9287\u20139294 (2017).","journal-title":"Mol. Med. Rep."},{"key":"85295_CR34","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.fertnstert.2016.11.025","volume":"107","author":"CF Yen","year":"2017","unstructured":"Yen, C. F. et al. Increased expression of integrin-linked kinase during decidualization regulates the morphological transformation of endometrial stromal cells. Fertil. Steril. 107, 803\u2013812 (2017).","journal-title":"Fertil. Steril."},{"key":"85295_CR35","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.acthis.2017.04.003","volume":"119","author":"B Zeng","year":"2017","unstructured":"Zeng, B., Liu, L., Wang, S. & Dai, Z. Ilk regulates mscs survival and angiogenesis partially through akt and mtor signaling pathways. Acta Histochem. 119, 400\u2013406 (2017).","journal-title":"Acta Histochem."},{"key":"85295_CR36","first-page":"3811","volume":"20","author":"X Zhang","year":"2019","unstructured":"Zhang, X., Qu, P., Zhao, H., Zhao, T. & Cao, N. Cox2 promotes epithelialmesenchymal transition and migration in osteosarcoma Mg63 cells via Pi3K\/Akt\/Nfkappab signaling. Mol. Med. Rep. 20, 3811\u20133819 (2019).","journal-title":"Mol. Med. Rep."},{"key":"85295_CR37","first-page":"1","volume":"31","author":"KA Devi","year":"2019","unstructured":"Devi, K. A. et al. Vietnamese coriander inhibits cell proliferation, survival and migration via suppression of Akt\/Mtor pathway in oral squamous cell carcinoma. J. Basic Clin. Physiol. Pharmacol. 31, 1\u201310 (2019).","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"85295_CR38","first-page":"6040","volume":"11","author":"J Xu","year":"2019","unstructured":"Xu, J. et al. Tumor-associated macrophages induce invasion and poor prognosis in human gastric cancer in a cyclooxygenase-2\/Mmp9-dependent manner. Am. J. Transl. Res. 11, 6040\u20136054 (2019).","journal-title":"Am. J. Transl. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85295-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85295-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85295-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:58:35Z","timestamp":1670047115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85295-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["85295"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-85295-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]},"assertion":[{"value":"8 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7186"}}