{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:24:33Z","timestamp":1777868673107,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112-2320-B-006-019-MY3"],"award-info":[{"award-number":["112-2320-B-006-019-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endometriosis is a common gynecological disorder affecting women of reproductive age, often leading to chronic pain, reduced quality of life, and infertility. It is characterized by ectopic endometrial growth within a hypoxic peritoneal environment. Autophagy, a cellular recycling pathway, is elevated in ectopic lesions. However, how hypoxia regulates autophagy to drive lesion development remains unclear. We found that inhibition of autophagy with chloroquine reduced stromal cell growth under hypoxia. The microRNA miR-21-5p, previously shown to be elevated by hypoxia in ectopic lesions, was examined and found to target cell division cycle 25A (CDC25A). Overexpression of miR-21-5p suppressed CDC25A. Under hypoxia, yes-associated protein 1 (YAP1) nuclear accumulation increased miR-21-5p, which in turn further reduced CDC25A expression. Silencing CDC25A enhanced autophagic flux, whereas pharmacologic inhibition of YAP1 with verteporfin restored CDC25A and p62 in mouse lesions and reduced lesion size. Collectively, these findings demonstrate that hypoxia activates YAP1-driven miR-21-5p, which represses CDC25A to promote autophagy and sustain lesion survival, highlighting the miR-21-5p\/CDC25A axis as a potential therapeutic target.<\/jats:p>","DOI":"10.1093\/molehr\/gaag020","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T12:43:37Z","timestamp":1774701817000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia-induced miR-21-5p promotes autophagy by downregulating CDC25A in endometriosis"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-1776","authenticated-orcid":false,"given":"Huan-Tzu","family":"Hou","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]},{"name":"Department of Physiology, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Chuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-5037","authenticated-orcid":false,"given":"Shih-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]},{"name":"Department of Physiology, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Hung","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital , Tainan,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-5554","authenticated-orcid":false,"given":"Meng-Hsing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital , Tainan,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-5813","authenticated-orcid":false,"given":"Shaw-Jenq","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, National Cheng Kung University , Tainan,","place":["Taiwan"]},{"name":"Department of Biomedical Sciences, College of Science, National Chung Cheng University , Minxiong, Chiayi County,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"2026043008215687600_gaag020-B1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.fertnstert.2015.02.007","article-title":"Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53 and heme oxygenase-1","volume":"103","author":"Allavena","year":"2015","journal-title":"Fertil Steril"},{"key":"2026043008215687600_gaag020-B2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1001\/jama.2025.2975","article-title":"Endometriosis: a review","volume":"334","author":"As-Sanie","year":"2025","journal-title":"JAMA"},{"key":"2026043008215687600_gaag020-B3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ncrna.2025.02.001","article-title":"Suppression of endometriosis by miRNA-34a via inhibition of matrix metalloproteinase-2: an alternative pathway to impede invasion","volume":"12","author":"Begum","year":"2025","journal-title":"Noncoding RNA Res"},{"key":"2026043008215687600_gaag020-B4","first-page":"1135","article-title":"MicroRNAs in endometriosis: biological function and emerging biomarker candidates","volume":"100","author":"Bjorkman","year":"2019","journal-title":"Biol Reprod"},{"key":"2026043008215687600_gaag020-B5","doi-asserted-by":"crossref","first-page":"szae079","DOI":"10.1093\/stcltm\/szae079","article-title":"Endostatin-expressing endometrial mesenchymal stem cells inhibit angiogenesis in endometriosis through the miRNA-21-5p\/TIMP3\/PI3K\/Akt\/mTOR pathway","volume":"14","author":"Cheng","year":"2025","journal-title":"Stem Cells Transl Med"},{"key":"2026043008215687600_gaag020-B6","doi-asserted-by":"crossref","first-page":"5770","DOI":"10.1038\/s41467-019-13659-4","article-title":"SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-coronavirus infection","volume":"10","author":"Gassen","year":"2019","journal-title":"Nat Commun"},{"key":"2026043008215687600_gaag020-B7","doi-asserted-by":"crossref","first-page":"616696","DOI":"10.3389\/fendo.2021.616696","article-title":"HMGB1 mediated inflammation and autophagy contribute to endometriosis","volume":"12","author":"Huang","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026043008215687600_gaag020-B9","doi-asserted-by":"crossref","first-page":"102635","DOI":"10.1016\/j.redox.2023.102635","article-title":"GSTP1-mediated S-glutathionylation of Pik3r1 is a redox hub that inhibits osteoclastogenesis through regulating autophagic flux","volume":"61","author":"Ji","year":"2023","journal-title":"Redox Biol"},{"key":"2026043008215687600_gaag020-B10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4103\/ejpi.EJPI-D-24-00032","article-title":"Association between uterine adenomyosis and infertility: role of axonemal alteration in apical endometria","volume":"67","author":"Khan","year":"2024","journal-title":"J Physiol Investig"},{"key":"2026043008215687600_gaag020-B11","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1177\/1933719119862050","article-title":"miR-451a inhibition reduces established endometriosis lesions in mice","volume":"26","author":"Li","year":"2019","journal-title":"Reprod Sci"},{"key":"2026043008215687600_gaag020-B12","doi-asserted-by":"crossref","first-page":"F19","DOI":"10.1530\/REP-20-0267","article-title":"Hypoxia and reproductive health: the role of hypoxia in the development and progression of endometriosis","volume":"161","author":"Li","year":"2021","journal-title":"Reproduction"},{"key":"2026043008215687600_gaag020-B13","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/path.4922","article-title":"Targeting hypoxia-mediated YAP1 nuclear translocation ameliorates pathogenesis of endometriosis without compromising maternal fertility","volume":"242","author":"Lin","year":"2017","journal-title":"J Pathol"},{"key":"2026043008215687600_gaag020-B14","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/humrep\/dead071","article-title":"Targeting YAP1 ameliorates progesterone resistance in endometriosis","volume":"38","author":"Lin","year":"2023","journal-title":"Hum Reprod"},{"key":"2026043008215687600_gaag020-B15","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1007\/s12035-023-03735-8","article-title":"Usf2 deficiency promotes autophagy to alleviate cerebral ischemia-reperfusion injury through suppressing YTHDF1-m6A-mediated Cdc25A translation","volume":"61","author":"Liu","year":"2024","journal-title":"Mol Neurobiol"},{"key":"2026043008215687600_gaag020-B16","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/biolre\/ioy128","article-title":"Autophagy contributes to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis","volume":"99","author":"Liu","year":"2018","journal-title":"Biol Reprod"},{"key":"2026043008215687600_gaag020-B17","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/jcmm.13947","article-title":"Long non-coding RNA MALAT1 mediates hypoxia-induced pro-survival autophagy of endometrial stromal cells in endometriosis","volume":"23","author":"Liu","year":"2019","journal-title":"J Cell Mol Med"},{"key":"2026043008215687600_gaag020-B18","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1530\/REP-16-0643","article-title":"Hypoxia-inducible factor-1alpha promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis","volume":"153","author":"Liu","year":"2017","journal-title":"Reproduction"},{"key":"2026043008215687600_gaag020-B19","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/s41419-023-06154-8","article-title":"Autophagy: regulator of cell death","volume":"14","author":"Liu","year":"2023","journal-title":"Cell Death Dis"},{"key":"2026043008215687600_gaag020-B20","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1111\/jog.15526","article-title":"miR-297 inhibits expression of progesterone receptor and decidualization in eutopic endometria of endometriosis","volume":"49","author":"Liu","year":"2023","journal-title":"J Obstet Gynaecol Res"},{"key":"2026043008215687600_gaag020-B21","doi-asserted-by":"crossref","first-page":"e2005970","DOI":"10.1371\/journal.pbio.2005970","article-title":"CellProfiler 3.0: next-generation image processing for biology","volume":"16","author":"McQuin","year":"2018","journal-title":"PLoS Biol"},{"key":"2026043008215687600_gaag020-B22","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1093\/humrep\/dead216","article-title":"The role of small extracellular vesicle-miRNAs in endometriosis","volume":"38","author":"Nazri","year":"2023","journal-title":"Hum Reprod"},{"key":"2026043008215687600_gaag020-B23","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1177\/1933719116681519","article-title":"Serum miR-451a levels are significantly elevated in women with endometriosis and recapitulated in baboons (Papio anubis) with experimentally-induced disease","volume":"24","author":"Nothnick","year":"2017","journal-title":"Reprod Sci"},{"key":"2026043008215687600_gaag020-B24","doi-asserted-by":"crossref","first-page":"e2059","DOI":"10.1038\/cddis.2015.361","article-title":"Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis","volume":"7","author":"Ruiz","year":"2016","journal-title":"Cell Death Dis"},{"key":"2026043008215687600_gaag020-B8","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am J Obstet Gynecol"},{"key":"2026043008215687600_gaag020-B25","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0002-9378(40)91238-8","article-title":"The development of the implantation theory for the origin of peritoneal endometriosis","volume":"40","author":"Sampson","year":"1940","journal-title":"Am J Obstet Gynecol"},{"key":"2026043008215687600_gaag020-B26","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.fertnstert.2012.10.051","article-title":"Targeting of syndecan-1 by micro-ribonucleic acid miR-10b modulates invasiveness of endometriotic cells via dysregulation of the proteolytic milieu and interleukin-6 secretion","volume":"99","author":"Schneider","year":"2013","journal-title":"Fertil Steril"},{"key":"2026043008215687600_gaag020-B27","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1210\/jc.2016-1120","article-title":"Activated Hippo\/Yes-associated protein pathway promotes cell proliferation and anti-apoptosis in endometrial stromal cells of endometriosis","volume":"101","author":"Song","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2026043008215687600_gaag020-B28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00109-024-02483-z","article-title":"Exosomal miR-21-5p derived from endometrial stromal cells promotes angiogenesis by targeting TIMP3 in ovarian endometrial cysts","volume":"102","author":"Sun","year":"2024","journal-title":"J Mol Med (Berl)"},{"key":"2026043008215687600_gaag020-B29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11010-016-2693-2","article-title":"Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies","volume":"416","author":"Sur","year":"2016","journal-title":"Mol Cell Biochem"},{"key":"2026043008215687600_gaag020-B30","doi-asserted-by":"crossref","first-page":"5765","DOI":"10.1210\/jcem.86.12.8082","article-title":"Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells","volume":"86","author":"Tsai","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2026043008215687600_gaag020-B31","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1093\/humrep\/dez116","article-title":"Plasma miRNAs as biomarkers for endometriosis","volume":"34","author":"Vanhie","year":"2019","journal-title":"Hum Reprod"},{"key":"2026043008215687600_gaag020-B32","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41419-021-04342-y","article-title":"Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis"},{"key":"2026043008215687600_gaag020-B33","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/jog.13900","article-title":"Hypoxia: the force of endometriosis","volume":"45","author":"Wu","year":"2019","journal-title":"J Obstet Gynaecol Res"},{"key":"2026043008215687600_gaag020-B34","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tjog.2012.01.010","article-title":"Estrogen receptor expression affected by hypoxia inducible factor-1alpha in stromal cells from patients with endometriosis","volume":"51","author":"Wu","year":"2012","journal-title":"Taiwan J Obstet Gynecol"},{"key":"2026043008215687600_gaag020-B35","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/kjm2.12626","article-title":"METTL3 is aberrantly expressed in endometriosis and suppresses proliferation, invasion, and migration of endometrial stromal cells","volume":"39","author":"Zhang","year":"2023","journal-title":"Kaohsiung J Med Sci"},{"key":"2026043008215687600_gaag020-B36","doi-asserted-by":"crossref","first-page":"149338","DOI":"10.1016\/j.bbrc.2023.149338","article-title":"Resveratrol protected against the development of endometriosis by promoting ferroptosis through miR-21-3p\/p53\/SLC7A11 signaling pathway","volume":"692","author":"Zou","year":"2024","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Molecular Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molehr\/advance-article-pdf\/doi\/10.1093\/molehr\/gaag020\/67695280\/gaag020.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/32\/2\/gaag020\/67695280\/gaag020.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/32\/2\/gaag020\/67695280\/gaag020.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:22:08Z","timestamp":1777551728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molehr\/article\/doi\/10.1093\/molehr\/gaag020\/8566399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/molehr\/gaag020","relation":{},"ISSN":["1360-9947","1460-2407"],"issn-type":[{"value":"1360-9947","type":"print"},{"value":"1460-2407","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"gaag020"}}