{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:42:36Z","timestamp":1791895356515,"version":"4.3.4"},"reference-count":29,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>MiRNAs play an important role in spermatogonial stem cells (SSCs). The purpose of this study was to investigate the basic function of miR-22-5p in cryptorchidism. The results of RT-PCR, western blot, and immunohistochemistry showed that miR-22-5p was increased while EZH2 decreased in the testicular tissues of patients with cryptorchidism. Overexpression of miR-22-5p inhibited the proliferation of SSCs, increased cell apoptosis rate, and reduced expression of SSC marker proteins (GDNF and DAZL); however, knockout of miR-22-5p has the opposite effect. The Luciferase reporter gene assays demonstrated that EZH2 is a direct target of miR-22-5p. Moreover, EZH2 overexpression could reverse the effect of miR-22-5p mimic on SSCs\u2019 proliferation, apoptosis, and expression of SSC marker proteins. Our results demonstrated that miR-22-5p regulates SSCs\u2019 self-renewal by targeting EZH2, which indicated that miR-22-5p may serve as a biological marker for the treatment of infertility caused by cryptorchidism.<\/jats:p>","DOI":"10.1515\/med-2022-0429","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T21:04:42Z","timestamp":1647723882000},"page":"556-565","source":"Crossref","is-referenced-by-count":12,"title":["miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2"],"prefix":"10.1515","volume":"17","author":[{"given":"Wenqiang","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230001 , Anhui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrician, Binhu District of Hefei First People\u2019s Hospital (The Third Affiliated Hospital of Anhui Medical University) , Hefei 230000 , Anhui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230001 , Anhui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"2022120618373756655_j_med-2022-0429_ref_001","doi-asserted-by":"crossref","unstructured":"Gurney J, McGlynn K, Stanley J, Merriman T, Signal V, Shaw C, et al. Risk factors for cryptorchidism. Nat Rev Urol. 2017;14(9):534\u201348. 10.1038\/nrurol.2017.90.","DOI":"10.1038\/nrurol.2017.90"},{"key":"2022120618373756655_j_med-2022-0429_ref_002","doi-asserted-by":"crossref","unstructured":"Hughes I, Acerini C. Factors controlling testis descent. Eur J Endocrinol. 2008;159(Suppl 1):S75\u201382. 10.1530\/EJE-08-0458.","DOI":"10.1530\/EJE-08-0458"},{"key":"2022120618373756655_j_med-2022-0429_ref_003","doi-asserted-by":"crossref","unstructured":"M\u00e4kel\u00e4 JA, Koskenniemi JJ, Virtanen HE, Toppari J. Testis Development. Endocr Rev. 2019;40(4):857\u2013905. 10.1210\/er.2018-00140.","DOI":"10.1210\/er.2018-00140"},{"key":"2022120618373756655_j_med-2022-0429_ref_004","doi-asserted-by":"crossref","unstructured":"Kanatsu-Shinohara M, Shinohara T. Spermatogonial stem cell self-renewal and development. Annu Rev Cell Dev Biol. 2013;29:163\u201387. 10.1146\/annurev-cellbio-101512-122353.","DOI":"10.1146\/annurev-cellbio-101512-122353"},{"key":"2022120618373756655_j_med-2022-0429_ref_005","doi-asserted-by":"crossref","unstructured":"M\u00e4kel\u00e4 J, Hobbs R. Molecular regulation of spermatogonial stem cell renewal and differentiation. Reproduction. 2019;158(5):R169\u201387. 10.1530\/REP-18-0476.","DOI":"10.1530\/REP-18-0476"},{"key":"2022120618373756655_j_med-2022-0429_ref_006","doi-asserted-by":"crossref","unstructured":"Subash S, Kumar P. Spermatogonial stem cells: a story of self-renewal and differentiation. Front Biosci (Landmark Ed). 2021;26:163\u2013205. 10.2741\/4891.","DOI":"10.2741\/4891"},{"key":"2022120618373756655_j_med-2022-0429_ref_007","doi-asserted-by":"crossref","unstructured":"Divisato G, Passaro F, Russo T, Parisi S. The key role of microRNAs in self-renewal and differentiation of embryonic stem cells. Int J Mol Sci. 2020;21(17):6285. 10.3390\/ijms21176285.","DOI":"10.3390\/ijms21176285"},{"key":"2022120618373756655_j_med-2022-0429_ref_008","doi-asserted-by":"crossref","unstructured":"Chen W, Cui Y, Ning M, Zhang H, Yin C, He Z. The mechanisms and functions of microRNAs in mediating the fate determinations of human spermatogonial stem cells and Sertoli cells. Semin Cell Dev Biol. 2022;121:32\u20139. 10.1016\/j.semcdb.2021.05.003.","DOI":"10.1016\/j.semcdb.2021.05.003"},{"key":"2022120618373756655_j_med-2022-0429_ref_009","doi-asserted-by":"crossref","unstructured":"Proc\u00f3pio M, de Avelar G, Costa G, Lacerda S, Resende R, de Fran\u00e7a L. MicroRNAs in Sertoli cells: implications for spermatogenesis and fertility. Cell Tissue Res. 2017;370(3):335\u201346. 10.1007\/s00441-017-2667-z.","DOI":"10.1007\/s00441-017-2667-z"},{"key":"2022120618373756655_j_med-2022-0429_ref_010","doi-asserted-by":"crossref","unstructured":"Kotaja N. MicroRNAs and spermatogenesis. Fertil Steril. 2014;101(6):1552\u201362. 10.1016\/j.fertnstert.2014.04.025.","DOI":"10.1016\/j.fertnstert.2014.04.025"},{"key":"2022120618373756655_j_med-2022-0429_ref_011","doi-asserted-by":"crossref","unstructured":"Li C, Yang B, Pan P, Ma Q, Wu Y, Zhang Z, et al. MicroRNA-130a inhibits spermatogenesis by directly targeting androgen receptor in mouse Sertoli cells. Mol Reprod Dev. 2018;85(10):768\u201377. 10.1002\/mrd.23058.","DOI":"10.1002\/mrd.23058"},{"key":"2022120618373756655_j_med-2022-0429_ref_012","doi-asserted-by":"crossref","unstructured":"Wang Y, Li X, Gong X, Zhao Y, Wu J. MicroRNA-322 regulates self-renewal of mouse spermatogonial stem cells through. Int J Biol Sci. 2019;15(4):857\u201369. 10.7150\/ijbs.30611.","DOI":"10.7150\/ijbs.30611"},{"key":"2022120618373756655_j_med-2022-0429_ref_013","doi-asserted-by":"crossref","unstructured":"Khanehzad M, Nourashrafeddin S, Abolhassani F, Kazemzadeh S, Madadi S, Shiri E, et al. MicroRNA-30a-5p promotes differentiation in neonatal mouse spermatogonial stem cells (SSCs). Reprod Biol Endocrinol. 2021;19(1):85. 10.1186\/s12958-021-00758-5.","DOI":"10.1186\/s12958-021-00758-5"},{"key":"2022120618373756655_j_med-2022-0429_ref_014","doi-asserted-by":"crossref","unstructured":"Fu H, Zhou F, Yuan Q, Zhang W, Qiu Q, Yu X, et al. MiRNA-31-5p mediates the proliferation and apoptosis of human spermatogonial stem cells via targeting JAZF1 and Cyclin A2. Mol Ther Nucleic Acids. 2019;14:90\u2013100. 10.1016\/j.omtn.2018.11.004.","DOI":"10.1016\/j.omtn.2018.11.004"},{"key":"2022120618373756655_j_med-2022-0429_ref_015","doi-asserted-by":"crossref","unstructured":"Zhou F, Chen W, Cui Y, Liu B, Yuan Q, Li Z, et al. MiRNA-122-5p stimulates the proliferation and DNA synthesis and inhibits the early apoptosis of human spermatogonial stem cells by targeting CBL and competing with lncRNA CASC7. Aging (Albany NY). 2020;12(24):25528\u201346. 10.18632\/aging.104158.","DOI":"10.18632\/aging.104158"},{"key":"2022120618373756655_j_med-2022-0429_ref_016","doi-asserted-by":"crossref","unstructured":"Wang Y, Chang W, Zhang Y, Zhang L, Ding H, Qi H, et al. Circulating miR-22-5p and miR-122-5p are promising novel biomarkers for diagnosis of acute myocardial infarction. J Cell Physiol. 2019;234(4):4778\u201386. 10.1002\/jcp.27274.","DOI":"10.1002\/jcp.27274"},{"key":"2022120618373756655_j_med-2022-0429_ref_017","doi-asserted-by":"crossref","unstructured":"Li H, Zhang P, Li F, Yuan G, Wang X, Zhang A, et al. Plasma miR-22-5p, miR-132-5p, and miR-150-3p are associated with acute myocardial infarction. Biomed Res Int. 2019;2019:5012648. 10.1155\/2019\/5012648.","DOI":"10.1155\/2019\/5012648"},{"key":"2022120618373756655_j_med-2022-0429_ref_018","doi-asserted-by":"crossref","unstructured":"Jusoh AR, Mohan SV, Ping TL, Tengku Din TADAAB, Haron J, Romli RC, et al. Plasma circulating mirnas profiling for identification of potential breast cancer early detection biomarkers. Asian Pac J Cancer Prev. 2021;22(5):1375\u201381. 10.31557\/APJCP.2021.22.5.1375.","DOI":"10.31557\/APJCP.2021.22.5.1375"},{"key":"2022120618373756655_j_med-2022-0429_ref_019","doi-asserted-by":"crossref","unstructured":"Wang J, Zhang H, Zhou X, Wang T, Zhang J, Zhu W, et al. Five serum-based miRNAs were identified as potential diagnostic biomarkers in gastric cardia adenocarcinoma. Cancer Biomark. 2018;23(2):193\u2013203. 10.3233\/CBM-181258.","DOI":"10.3233\/CBM-181258"},{"key":"2022120618373756655_j_med-2022-0429_ref_020","doi-asserted-by":"crossref","unstructured":"Dakterzada F, Targa A, Ben\u00edtez I, Romero-ElKhayat L, de Gonzalo-Calvo D, Torres G, et al. Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer\u2019s disease. Alzheimers Res Ther. 2020;12(1):163. 10.1186\/s13195-020-00735-x.","DOI":"10.1186\/s13195-020-00735-x"},{"key":"2022120618373756655_j_med-2022-0429_ref_021","doi-asserted-by":"crossref","unstructured":"Ragni E, Perucca Orfei C, De Luca P, Vigan\u00f2 M, Colombini A, Lugano G, et al. miR-22-5p and miR-29a-5p are reliable reference genes for analyzing extracellular vesicle-associated miRNAs in adipose-derived mesenchymal stem cells and are stable under inflammatory priming mimicking osteoarthritis condition. Stem Cell Rev Rep. 2019;15(5):743\u201354. 10.1007\/s12015-019-09899-y.","DOI":"10.1007\/s12015-019-09899-y"},{"key":"2022120618373756655_j_med-2022-0429_ref_022","doi-asserted-by":"crossref","unstructured":"Moritoki Y, Hayashi Y, Mizuno K, Kamisawa H, Nishio H, Kurokawa S, et al. Expression profiling of microRNA in cryptorchid testes: miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1. J Urol. 2014;191(4):1174\u201380. 10.1016\/j.juro.2013.10.137.","DOI":"10.1016\/j.juro.2013.10.137"},{"key":"2022120618373756655_j_med-2022-0429_ref_023","doi-asserted-by":"crossref","unstructured":"Jin C, Zhang Y, Wang Z, Wang X, Sun T, Li X, et al. EZH2 deletion promotes spermatogonial differentiation and apoptosis. Reproduction. 2017;154(5):615\u201325. 10.1530\/REP-17-0302.","DOI":"10.1530\/REP-17-0302"},{"key":"2022120618373756655_j_med-2022-0429_ref_024","doi-asserted-by":"crossref","unstructured":"Cai Y, Deng M, Liu Z, Zhang G, Pang J, An S, et al. EZH2 expression and its role in spermatogonial stem cell self-renewal in goats. Theriogenology. 2020;155:222\u201331. 10.1016\/j.theriogenology.2020.06.013.","DOI":"10.1016\/j.theriogenology.2020.06.013"},{"key":"2022120618373756655_j_med-2022-0429_ref_025","doi-asserted-by":"crossref","unstructured":"Yan H, Gao Y, Ding Q, Liu J, Li Y, Jin M, et al. Exosomal micro RNAs derived from dermal papilla cells mediate hair follicle stem cell proliferation and differentiation. Int J Biol Sci. 2019;15(7):1368\u201382. 10.7150\/ijbs.33233.","DOI":"10.7150\/ijbs.33233"},{"key":"2022120618373756655_j_med-2022-0429_ref_026","doi-asserted-by":"crossref","unstructured":"Collinson A, Collier A, Morgan N, Sienerth A, Chandra T, Andrews S, et al. Deletion of the polycomb-group protein EZH2 leads to compromised self-renewal and differentiation defects in human embryonic stem cells. Cell Rep. 2016;17(10):2700\u201314. 10.1016\/j.celrep.2016.11.032.","DOI":"10.1016\/j.celrep.2016.11.032"},{"key":"2022120618373756655_j_med-2022-0429_ref_027","doi-asserted-by":"crossref","unstructured":"Yu Y, Deng P, Yu B, Szymanski J, Aghaloo T, Hong C, et al. Inhibition of EZH2 promotes human embryonic stem cell differentiation into mesoderm by reducing H3K27me3. Stem Cell Reports. 2017;9(3):752\u201361. 10.1016\/j.stemcr.2017.07.016.","DOI":"10.1016\/j.stemcr.2017.07.016"},{"key":"2022120618373756655_j_med-2022-0429_ref_028","doi-asserted-by":"crossref","unstructured":"Hinz S, Magheli A, Weikert S, Schulze W, Krause H, Schrader M, et al. Deregulation of EZH2 expression in human spermatogenic disorders and testicular germ cell tumors. World J Urol. 2010;28(5):631\u20135. 10.1007\/s00345-009-0498-6.","DOI":"10.1007\/s00345-009-0498-6"},{"key":"2022120618373756655_j_med-2022-0429_ref_029","doi-asserted-by":"crossref","unstructured":"Tremblay-LeMay R, Rastgoo N, Pourabdollah M, Chang H. EZH2 as a therapeutic target for multiple myeloma and other haematological malignancies. Biomark Res. 2018;6:34. 10.1186\/s40364-018-0148-5.","DOI":"10.1186\/s40364-018-0148-5"}],"container-title":["Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2022-0429\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2022-0429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T22:59:00Z","timestamp":1670367540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2022-0429\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,3,28]]},"published-print":{"date-parts":[[2022,3,28]]}},"alternative-id":["10.1515\/med-2022-0429"],"URL":"https:\/\/doi.org\/10.1515\/med-2022-0429","relation":{},"ISSN":["2391-5463"],"issn-type":[{"value":"2391-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]}}}