{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T13:10:45Z","timestamp":1769346645757,"version":"3.49.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"U.S. Department of Health &amp; Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD069043"],"award-info":[{"award-number":["HD069043"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"U.S. Department of Health &amp; Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD073733"],"award-info":[{"award-number":["HD073733"]}],"id":[{"id":"10.13039\/100009633","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>Endometriosis is an inflammatory condition in which endometrial tissue grows in ectopic locations. Survival and growth of these ectopic lesions is associated with pain and infertility. MicroRNAs (miRNAs) have been postulated to play a role in the pathophysiology of the disease and we have previously demonstrated expression of miR-451 in human endometriotic lesion tissue. Here we report elevated expression of the miR-144-3p\/miR-451a cluster in human endometriotic lesion tissue. Use of an endometriotic epithelial cell line (12Z) in which the miRNA processing enzyme, DROSHA, was knocked down resulted in an enrichment in the primary (pri) form of miR-144-3p but not that of pri-miR-451a. Using an experimental mouse model of endometriosis in which ectopic endometriotic lesions were deficient for both of these miRNAs revealed that miR-451a, but not miR-144-3p may be derived from exogenous sources such as the circulation\/erythrocytes. Together, these data suggest that the miR-144-3p\/miR-451a cluster is expressed in human endometriotic lesion tissue, the level of expression correlates with survival status of the lesion tissue and that miR-451a, but not miR-144-3p may be derived from exogenous sources such as erythrocytes.<\/jats:p>","DOI":"10.1038\/s41598-019-45243-7","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T12:04:56Z","timestamp":1560945896000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human endometriotic lesion expression of the miR-144-3p\/miR-451a cluster, its correlation with markers of cell survival and origin of lesion content"],"prefix":"10.1038","volume":"9","author":[{"given":"Warren B.","family":"Nothnick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Swan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Flyckt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Falcone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"45243_CR1","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","volume":"364","author":"LC Giudice","year":"2004","unstructured":"Giudice, L. C. & Kao, L. C. Endometriosis. Lancet. 364, 1789\u20131799 (2004).","journal-title":"Lancet."},{"key":"45243_CR2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2147\/IJWH.S119729","volume":"16","author":"AS Lagan\u00e0","year":"2017","unstructured":"Lagan\u00e0, A. S. et al. Anxiety and depression in patients with endometriosis: impact and management challenges. Int. J. Womens Health. 16, 323\u2013330 (2017).","journal-title":"Int. J. Womens Health."},{"key":"45243_CR3","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/0167482X.2016.1244185","volume":"38","author":"SG Vitale","year":"2017","unstructured":"Vitale, S. G., La Rosa, V. L., Rapisarda, A. M. C. & Lagan\u00e0, A. S. Impact of endometriosis on quality of life and psychological well-being. J. Psychosom. Obstet. Gynecol. 38, 317\u2013319 (2017).","journal-title":"J. Psychosom. Obstet. Gynecol."},{"key":"45243_CR4","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.jogc.2016.09.008","volume":"38","author":"SG Vitale","year":"2016","unstructured":"Vitale, S. G., Petrosino, B., La Rosa, V. L., Rapisarda, A. M. & Lagan\u00e0, A. S. A systematic review of the association between psychiatric disturbances and endometriosis. J. Obstet. Gynecol. Can. 38, 1079\u20131080 (2016).","journal-title":"J. Obstet. Gynecol. Can."},{"key":"45243_CR5","first-page":"151","volume":"64","author":"J Halme","year":"1984","unstructured":"Halme, J., Hammond, M. G., Hulka, J. F., Raj, S. G. & Talbert, L. M. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet. Gynecol. 64, 151\u2013154 (1984).","journal-title":"Obstet. Gynecol."},{"key":"45243_CR6","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1111\/j.1471-0528.1986.tb07995.x","volume":"93","author":"DT Liu","year":"1986","unstructured":"Liu, D. T. & Hitchcock, A. Endometriosis: its association with retrograde menstruation, dysmenorrhoea and tubal pathology. Br. J. Obstet. Gynaecol. 93, 859\u2013862 (1986).","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"45243_CR7","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.autrev.2018.03.017","volume":"17","author":"T Zhang","year":"2018","unstructured":"Zhang, T., De Carolis, C., Man, G. C. W. & Wang, C. C. The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmune Rev. 17, 945\u2013955 (2018).","journal-title":"Autoimmune Rev."},{"key":"45243_CR8","first-page":"3123","volume":"18","author":"M Ba\u0142kowiec","year":"2018","unstructured":"Ba\u0142kowiec, M., Maksym, R. B. & W\u0142odarski, P. K. The bimodal role of matrix metalloproteinases and their inhibitors in etiology and pathogenesis of endometriosis (Review). Mol. Med. Rep. 18, 3123\u20133136 (2018).","journal-title":"Mol. Med. Rep."},{"key":"45243_CR9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.12688\/f1000research","volume":"17","author":"W Nothnick","year":"2016","unstructured":"Nothnick, W. & Alali, Z. Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment. F1000Res. 17, 5, https:\/\/doi.org\/10.12688\/f1000research (2016).","journal-title":"F1000Res."},{"key":"45243_CR10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.bpobgyn.2018.01.006","volume":"50","author":"BG Patel","year":"2018","unstructured":"Patel, B. G. et al. Pathogenesis of endometriosis: Interaction between endocrine and inflammatory pathways. Best Pract. Res. Clin. Obstet. Gynaecol. 50, 50\u201360 (2018).","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"45243_CR11","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1177\/1933719116687661","volume":"25","author":"AS Lagan\u00e0","year":"2018","unstructured":"Lagan\u00e0, A. S., Salmeri, F. M., Vitale, S. G., Triolo, O. & G\u00f6tte, M. Stem cell trafficking during endometriosis: may epigenetics play a pivotal role? Reprod. Sci. 25, 978\u2013979 (2018).","journal-title":"Reprod. Sci."},{"key":"45243_CR12","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/s00404-016-4195-6","volume":"294","author":"V Vetvicka","year":"2016","unstructured":"Vetvicka, V. et al. Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives. Arch. Gynecol. Obstet. 294, 897\u2013904 (2016).","journal-title":"Arch. Gynecol. Obstet."},{"key":"45243_CR13","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/humupd\/dmy014","volume":"24","author":"K Panir","year":"2018","unstructured":"Panir, K., Schjenken, J. E., Robertson, S. A. & Hull, M. L. Non-coding RNAs in endometriosis: a narrative review. Hum. Reprod. Update. 24, 497\u2013515 (2018).","journal-title":"Hum. Reprod. Update."},{"key":"45243_CR14","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116, 281\u2013297 (2004).","journal-title":"Cell."},{"key":"45243_CR15","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/j.1399-0004.2008.01076.x","volume":"74","author":"AE Erson","year":"2008","unstructured":"Erson, A. E. & Petty, E. M. MicroRNAs in development and disease. Clin. Genet. 74, 296\u2013306 (2008).","journal-title":"Clin. Genet."},{"key":"45243_CR16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1210\/me.2008-0387","volume":"23","author":"EM Ohlsson Teague","year":"2009","unstructured":"Ohlsson Teague, E. M. et al. MicroRNA-regulated pathways associated with endometriosis. Mol. Endocrinol. 23, 265\u2013275 (2009).","journal-title":"Mol. Endocrinol."},{"key":"45243_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2010\/369549","volume":"2010","author":"Nicoletta Filigheddu","year":"2010","unstructured":"Filigheddu, N. et al. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol. 2010, https:\/\/doi.org\/10.1155\/2010\/369549 (2010).","journal-title":"Journal of Biomedicine and Biotechnology"},{"key":"45243_CR18","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1210\/me.2010-0371","volume":"25","author":"SM Hawkins","year":"2011","unstructured":"Hawkins, S. M. et al. Functional microRNA involved in endometriosis. Mol. Endocrinol. 25, 821\u2013832 (2011).","journal-title":"Mol. Endocrinol."},{"key":"45243_CR19","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1093\/humrep\/deu019","volume":"29","author":"A Braza-Boils","year":"2014","unstructured":"Braza-Boils, A. et al. MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum. Reprod. 29, 978\u2013988 (2014).","journal-title":"Hum. Reprod."},{"key":"45243_CR20","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1093\/biolre\/ioy019","volume":"98","author":"ME Haikalis","year":"2018","unstructured":"Haikalis, M. E., Wessels, J. M., Leyland, N. A., Agarwal, S. K. & Foster, W. G. MicroRNA expression pattern differs depending on endometriosis lesion type. Biol. Reprod. 98, 623\u2013633 (2018).","journal-title":"Biol. Reprod."},{"key":"45243_CR21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.7554\/eLife05005","volume":"12","author":"V Agarwal","year":"2015","unstructured":"Agarwal, V., Bell, G. W., Nam, J. W. & Bartel, D. P. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 12, 4, https:\/\/doi.org\/10.7554\/eLife05005 (2015).","journal-title":"Elife."},{"key":"45243_CR22","doi-asserted-by":"publisher","first-page":"D360","DOI":"10.1093\/nar\/gkx1144","volume":"46","author":"T Tokar","year":"2018","unstructured":"Tokar, T. et al. mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res. 46, D360\u2013D370 (2018).","journal-title":"Nucleic Acids Res."},{"key":"45243_CR23","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1093\/humrep\/dev005","volume":"30","author":"A Graham","year":"2015","unstructured":"Graham, A., Falcone, T. & Nothnick, W. B. The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Hum. Reprod. 30, 642\u2013652 (2015).","journal-title":"Hum. Reprod."},{"key":"45243_CR24","first-page":"2881","volume":"30","author":"NR Joshi","year":"2015","unstructured":"Joshi, N. R. et al. Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio Anubis) with endometriosis. Hum. Reprod. 30, 2881\u2013291 (2015).","journal-title":"Hum. Reprod."},{"key":"45243_CR25","doi-asserted-by":"publisher","first-page":"3333","DOI":"10.1073\/pnas.0712312105","volume":"105","author":"LC Dore","year":"2008","unstructured":"Dore, L. C. et al. GATA-1 regulated microRNA locus essential for erythropoiesis. Proc. Natl. Acad. Sci. USA. 105, 3333\u20133338 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"45243_CR26","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.ejogrb.2004.02.007","volume":"116","author":"L Cobellis","year":"2004","unstructured":"Cobellis, L. et al. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 116, 100\u2013102 (2004).","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"45243_CR27","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1093\/humrep\/den315","volume":"23","author":"C Olivares","year":"2008","unstructured":"Olivares, C. et al. Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hum. Reprod. 23, 2701\u20132708 (2008).","journal-title":"Hum. Reprod."},{"key":"45243_CR28","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1210\/jc.2013-2950","volume":"99","author":"P Santulli","year":"2014","unstructured":"Santulli, P. et al. Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissue. J. Clin. Endocrinol. Metab. 99, 881\u2013890 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"45243_CR29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1600-0897.1995.tb00968.x","volume":"34","author":"JA Keenan","year":"1995","unstructured":"Keenan, J. A., Chen, T. T., Chadwell, N. L., Torry, D. S. & Caudle, M. R. IL-1beta, TNF-alpha, and IL-2 in the peritoneal fluid and macrophage-conditioned media of women with endometriosis. Am. J. Reprod. Immunol. 34, 381\u201385 (1995).","journal-title":"Am. J. Reprod. Immunol."},{"key":"45243_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000010269","volume":"50","author":"A Bergqvist","year":"2000","unstructured":"Bergqvist, A. et al. Production of interleukins 1beta, 6 and 8 and tumor necrosis factor alpha in separated and cultured endometrial and endometriotic stromal and epithelial cells. Gynecol. Obstet. Invest. 50, 1\u20136 (2000).","journal-title":"Gynecol. Obstet. Invest."},{"key":"45243_CR31","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0015-0282(99)00496-3","volume":"73","author":"T Tsudo","year":"2000","unstructured":"Tsudo, T. et al. Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissue. Fertil. Steril. 73, 205\u2013211 (2000).","journal-title":"Fertil. Steril."},{"key":"45243_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mce.2014.12.007","volume":"402","author":"D Li","year":"2015","unstructured":"Li, D. et al. Down-regulation of miR-144 elecits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats. Mol. Cell Endocrinol. 402, 1\u201312 (2015).","journal-title":"Mol. Cell Endocrinol."},{"key":"45243_CR33","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.cyto.2018.03.043","volume":"108","author":"RD Li","year":"2018","unstructured":"Li, R. D. et al. MicroRNA-144 suppresses the expression of cytokines through targeting RANKL in the matured immune cells. Cytokine. 108, 197\u2013204 (2018).","journal-title":"Cytokine."},{"issue":"6","key":"45243_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/srep27914","volume":"14","author":"H Li","year":"2016","unstructured":"Li, H. et al. miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor. Sci. Rep. 14(6), 27914 (2016).","journal-title":"Sci. Rep."},{"key":"45243_CR35","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nature09092","volume":"465","author":"S Cheloufi","year":"2010","unstructured":"Cheloufi, S., Dos Santos, C. O., Chong, M. M. & Hannon, G. J. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 465, 584\u2013589 (2010).","journal-title":"Nature."},{"key":"45243_CR36","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1126\/science.1190809","volume":"328","author":"D Cifuentes","year":"2010","unstructured":"Cifuentes, D. et al. A novel miRNA processing pathway independent of Dicer requires Argonaute 2 catalytic activity. Science. 328, 1694\u20131698 (2010).","journal-title":"Science."},{"key":"45243_CR37","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1177\/1933719118766262","volume":"25","author":"WB Nothnick","year":"2018","unstructured":"Nothnick, W. B. et al. Macrophage migration inhibitory factor receptor, CD74, is overexpressed in human and baboon (Panio Anubis) endometriotic lesions and modulates endometriotic epithelial cell survival and interleukin-8 expression. Reprod. Sci. 25, 1557\u20131566 (2018).","journal-title":"Reprod. Sci."},{"key":"45243_CR38","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1016\/S0002-9440(10)63030-1","volume":"159","author":"A Zeitvogel","year":"2001","unstructured":"Zeitvogel, A., Baumann, R. & Starzinski-Powitz, A. Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am. J. Pathol. 159, 1839\u20131852 (2001).","journal-title":"Am. J. Pathol."},{"key":"45243_CR39","doi-asserted-by":"publisher","first-page":"e100336","DOI":"10.1371\/journal.pone.0100336","volume":"9","author":"WB Nothnick","year":"2014","unstructured":"Nothnick, W. B., Graham, A., Holbert, J. & Weiss, M. J. miR-451 deficiency is associated with altered endometrial fibrinogen alpha chain expression and reduced endometriotic implant establishment in an experimental mouse model. PLoS. One. 9, e100336 (2014).","journal-title":"PLoS. One."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45243-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45243-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45243-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T10:39:50Z","timestamp":1671273590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45243-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,19]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45243"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45243-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,19]]},"assertion":[{"value":"7 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2019","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":"8823"}}