{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:15:24Z","timestamp":1793171724350,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T00:00:00Z","timestamp":1729382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T00:00:00Z","timestamp":1729382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82301850"],"award-info":[{"award-number":["82301850"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2022106020"],"award-info":[{"award-number":["H2022106020"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-75178-7","type":"journal-article","created":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T10:01:43Z","timestamp":1729418503000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["ER stress-induced LINC00173 promotes the apoptosis of ovarian granulosa cells by regulating the HRK\/PI3K\/AKT pathway in polycystic ovary syndrome"],"prefix":"10.1038","volume":"14","author":[{"given":"Yuanyuan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyu","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"75178_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.962775","volume":"13","author":"X Feng","year":"2022","unstructured":"Feng, X. et al. Dendrobium officinale polysaccharide ameliorates polycystic ovary syndrome via regulating butyrate dependent gut\u2013brain\u2013ovary axis mechanism. Front. Endocrinol. (Lausanne) 13, 962775 (2022).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"75178_CR2","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12487","volume":"21","author":"M Harada","year":"2022","unstructured":"Harada, M. Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research. Reprod. Med. Biol. 21, e12487 (2022).","journal-title":"Reprod. Med. Biol."},{"key":"75178_CR3","doi-asserted-by":"crossref","unstructured":"Singh, S. et al. Polycystic ovary syndrome: Etiology, current management, and future therapeutics. J. Clin. Med. 12 (2023).","DOI":"10.3390\/jcm12041454"},{"key":"75178_CR4","doi-asserted-by":"publisher","first-page":"R79","DOI":"10.1530\/REP-18-0583","volume":"158","author":"AP Snider","year":"2019","unstructured":"Snider, A. P. & Wood, J. R. Obesity induces ovarian inflammation and reduces oocyte quality. Reproduction 158, R79\u2013R90 (2019).","journal-title":"Reproduction"},{"key":"75178_CR5","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1093\/humrep\/dead156","volume":"38","author":"HJ Teede","year":"2023","unstructured":"Teede, H. J. et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndromedagger. Hum. Reprod. 38, 1655\u20131679 (2023).","journal-title":"Hum. Reprod."},{"key":"75178_CR6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/rmb2.12292","volume":"19","author":"MH Alam","year":"2020","unstructured":"Alam, M. H. & Miyano, T. Interaction between growing oocytes and granulosa cells in vitro. Reprod. Med. Biol. 19, 13\u201323 (2020).","journal-title":"Reprod. Med. Biol."},{"key":"75178_CR7","doi-asserted-by":"crossref","unstructured":"Jozkowiak, M. et al. Endocrine disrupting chemicals in polycystic ovary syndrome: The relevant role of the theca and granulosa cells in the pathogenesis of the ovarian dysfunction. Cells 12 (2022).","DOI":"10.3390\/cells12010174"},{"key":"75178_CR8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1262\/jrd.2011-012","volume":"58","author":"F Matsuda","year":"2012","unstructured":"Matsuda, F., Inoue, N., Manabe, N. & Ohkura, S. Follicular growth and atresia in mammalian ovaries: Regulation by survival and death of granulosa cells. J. Reprod. Dev. 58, 44\u201350 (2012).","journal-title":"J. Reprod. Dev."},{"key":"75178_CR9","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","volume":"24","author":"JS Mattick","year":"2023","unstructured":"Mattick, J. S. et al. Long non-coding RNAs: Definitions, functions, challenges and recommendations. Nat. Rev. Mol. Cell Biol. 24, 430\u2013447 (2023).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"75178_CR10","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.tig.2017.08.002","volume":"33","author":"A Jandura","year":"2017","unstructured":"Jandura, A. & Krause, H. M. The new RNA world: Growing evidence for long noncoding RNA functionality. Trends Genet. 33, 665\u2013676 (2017).","journal-title":"Trends Genet."},{"key":"75178_CR11","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41556-019-0311-8","volume":"21","author":"RW Yao","year":"2019","unstructured":"Yao, R. W., Wang, Y. & Chen, L. L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 21, 542\u2013551 (2019).","journal-title":"Nat. Cell Biol."},{"key":"75178_CR12","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.ymthe.2020.11.018","volume":"29","author":"X Geng","year":"2021","unstructured":"Geng, X. et al. lnc-MAP3K13-7:1 inhibits ovarian GC proliferation in PCOS via DNMT1 downregulation-mediated CDKN1A promoter hypomethylation. Mol. Ther. 29, 1279\u20131293 (2021).","journal-title":"Mol. Ther."},{"key":"75178_CR13","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.omtn.2020.12.008","volume":"23","author":"J Huang","year":"2021","unstructured":"Huang, J. et al. Long non-coding RNA lnc-CCNL1-3:1 promotes granulosa cell apoptosis and suppresses glucose uptake in women with polycystic ovary syndrome. Mol. Ther. Nucleic Acids 23, 614\u2013628 (2021).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"75178_CR14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12929-021-00749-z","volume":"28","author":"J Zhen","year":"2021","unstructured":"Zhen, J. et al. Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381\/IGF1 axis. J. Biomed. Sci. 28, 53 (2021).","journal-title":"J. Biomed. Sci."},{"key":"75178_CR15","doi-asserted-by":"publisher","first-page":"10373","DOI":"10.1080\/21655979.2022.2053797","volume":"13","author":"L Chen","year":"2022","unstructured":"Chen, L. & Kong, C. LINC00173 regulates polycystic ovarian syndrome progression by promoting apoptosis and repressing proliferation in ovarian granulosa cells via the microRNA-124-3p (miR-124-3p)\/jagged canonical Notch ligand 1 (JAG1) pathway. Bioengineered 13, 10373\u201310385 (2022).","journal-title":"Bioengineered"},{"key":"75178_CR16","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","volume":"21","author":"C Hetz","year":"2020","unstructured":"Hetz, C., Zhang, K. & Kaufman, R. J. Mechanisms, regulation and functions of the unfolded protein response. Nat. Rev. Mol. Cell Biol. 21, 421\u2013438 (2020).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"75178_CR17","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1083\/jcb.201003138","volume":"189","author":"DT Rutkowski","year":"2010","unstructured":"Rutkowski, D. T. & Hegde, R. S. Regulation of basal cellular physiology by the homeostatic unfolded protein response. J. Cell Biol. 189, 783\u2013794 (2010).","journal-title":"J. Cell Biol."},{"key":"75178_CR18","doi-asserted-by":"publisher","first-page":"10824","DOI":"10.1038\/s41598-017-11252-7","volume":"7","author":"N Takahashi","year":"2017","unstructured":"Takahashi, N. et al. Activation of endoplasmic reticulum stress in granulosa cells from patients with polycystic ovary syndrome contributes to ovarian fibrosis. Sci. Rep. 7, 10824 (2017).","journal-title":"Sci. Rep."},{"key":"75178_CR19","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1177\/1933719116667606","volume":"24","author":"T Li","year":"2017","unstructured":"Li, T. et al. Role of the PI3K-Akt signaling pathway in the pathogenesis of polycystic ovary syndrome. Reprod. Sci. 24, 646\u2013655 (2017).","journal-title":"Reprod. Sci."},{"key":"75178_CR20","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s12958-020-00677-x","volume":"18","author":"Y Gong","year":"2020","unstructured":"Gong, Y. et al. Growth hormone activates PI3K\/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod. Biol. Endocrinol. 18, 121 (2020).","journal-title":"Reprod. Biol. Endocrinol."},{"key":"75178_CR21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12905-022-02154-6","volume":"23","author":"P Sun","year":"2023","unstructured":"Sun, P. et al. Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K\/AKT\/ERK signalling pathway. BMC Womens Health 23, 15 (2023).","journal-title":"BMC Womens Health"},{"key":"75178_CR22","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1210\/me.2003-0178","volume":"18","author":"CL Hu","year":"2004","unstructured":"Hu, C. L., Cowan, R. G., Harman, R. M. & Quirk, S. M. Cell cycle progression and activation of Akt kinase are required for insulin-like growth factor I-mediated suppression of apoptosis in granulosa cells. Mol. Endocrinol. 18, 326\u2013338 (2004).","journal-title":"Mol. Endocrinol."},{"key":"75178_CR23","first-page":"2113293","volume":"2022","author":"Y Zhang","year":"2022","unstructured":"Zhang, Y. et al. Curcumin inhibits hyperandrogen-induced IRE1alpha-XBP1 pathway activation by activating the PI3K\/AKT signaling in ovarian granulosa cells of PCOS model rats. Oxid. Med. Cell. Longev. 2022, 2113293 (2022).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"75178_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117025","volume":"318","author":"W Hu","year":"2024","unstructured":"Hu, W. et al. Chinese herbal medicine alleviates autophagy and apoptosis in ovarian granulosa cells induced by testosterone through PI3K\/AKT1\/FOXO1 pathway. J. Ethnopharmacol. 318, 117025 (2024).","journal-title":"J. Ethnopharmacol."},{"key":"75178_CR25","unstructured":"Sun, H. L. et al. Does endoplasmic reticulum stress stimulate the apoptosis of granulosa cells in polycystic ovary syndrome? J. Physiol. Pharmacol. 72 (2021)."},{"key":"75178_CR26","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.yexcr.2015.04.010","volume":"334","author":"Y Shen","year":"2015","unstructured":"Shen, Y. et al. The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK\/p62 signals: A survival mechanism in methotrexate-resistant choriocarcinoma cells. Exp. Cell Res. 334, 207\u2013218 (2015).","journal-title":"Exp. Cell Res."},{"key":"75178_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.779718","volume":"9","author":"Y Gao","year":"2021","unstructured":"Gao, Y. et al. USP25 regulates the proliferation and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by modulating the PI3K\/AKT pathway via deubiquitinating PTEN. Front. Cell Dev. Biol. 9, 779718 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"75178_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.154351","volume":"243","author":"S Ghafouri-Fard","year":"2023","unstructured":"Ghafouri-Fard, S. et al. A review on the role of LINC00173 in human cancers. Pathol. Res. Pract. 243, 154351 (2023).","journal-title":"Pathol. Res. Pract."},{"key":"75178_CR29","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3233\/CBM-201616","volume":"29","author":"Q Yang","year":"2020","unstructured":"Yang, Q. et al. Long intergenic noncoding RNA LINC00173 as a potential serum biomarker for diagnosis of non-small-cell lung cancer. Cancer Biomark. 29, 441\u2013451 (2020).","journal-title":"Cancer Biomark."},{"key":"75178_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.152994","volume":"216","author":"J Zhang","year":"2020","unstructured":"Zhang, J., Zhou, M., Zhao, X., Wang, G. & Li, J. Long noncoding RNA LINC00173 is downregulated in cervical cancer and inhibits cell proliferation and invasion by modulating the miR-182-5p\/FBXW7 axis. Pathol. Res. Pract. 216, 152994 (2020).","journal-title":"Pathol. Res. Pract."},{"key":"75178_CR31","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1089\/dna.2020.6103","volume":"40","author":"Q Li","year":"2021","unstructured":"Li, Q. et al. Long intergenic nonprotein coding RNA 173 inhibits tumor growth and promotes apoptosis by repressing sphingosine kinase 1 protein expression in pancreatic cancer. DNA Cell Biol. 40, 757\u2013775 (2021).","journal-title":"DNA Cell Biol."},{"key":"75178_CR32","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1515\/hmbci-2022-0051","volume":"44","author":"B Alexandre-Santos","year":"2023","unstructured":"Alexandre-Santos, B. et al. Potential role of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome. Horm. Mol. Biol. Clin. Investig. 44, 105\u2013112 (2023).","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"75178_CR33","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1210\/en.2018-00675","volume":"160","author":"JMK Azhary","year":"2019","unstructured":"Azhary, J. M. K. et al. Endoplasmic reticulum stress activated by androgen enhances apoptosis of granulosa cells via induction of death receptor 5 in PCOS. Endocrinology 160, 119\u2013132 (2019).","journal-title":"Endocrinology"},{"key":"75178_CR34","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1093\/emboj\/16.7.1686","volume":"16","author":"N Inohara","year":"1997","unstructured":"Inohara, N., Ding, L., Chen, S. & Nunez, G. harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). EMBO J. 16, 1686\u20131694 (1997).","journal-title":"EMBO J."},{"key":"75178_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2022.103638","volume":"152","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y., Pan, S. & Wu, X. Human umbilical cord mesenchymal stem cell-derived exosomes inhibit ovarian granulosa cells inflammatory response through inhibition of NF-kappaB signaling in polycystic ovary syndrome. J. Reprod. Immunol. 152, 103638 (2022).","journal-title":"J. Reprod. Immunol."},{"key":"75178_CR36","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s11010-023-04736-w","volume":"479","author":"W Tan","year":"2024","unstructured":"Tan, W. et al. Insights on the NF-kappaB system in polycystic ovary syndrome, attractive therapeutic targets. Mol. Cell. Biochem. 479, 467\u2013486 (2024).","journal-title":"Mol. Cell. Biochem."},{"key":"75178_CR37","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1002\/ptr.7749","volume":"37","author":"R Ji","year":"2023","unstructured":"Ji, R., Jia, F., Chen, X., Gao, Y. & Yang, J. Carnosol inhibits KGN cells oxidative stress and apoptosis and attenuates polycystic ovary syndrome phenotypes in mice through Keap1-mediated Nrf2\/HO-1 activation. Phytother. Res. 37, 1405\u20131421 (2023).","journal-title":"Phytother. Res."},{"key":"75178_CR38","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1093\/humrep\/deac067","volume":"37","author":"P Froment","year":"2022","unstructured":"Froment, P. et al. At the crossroads of fertility and metabolism: The importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism. Hum. Reprod. 37, 1207\u20131228 (2022).","journal-title":"Hum. Reprod."},{"key":"75178_CR39","doi-asserted-by":"crossref","unstructured":"Wang, Y. et al. Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1\/Nrf2 pathway. Mol. Hum. Reprod. 27 (2021).","DOI":"10.1093\/molehr\/gaaa081"},{"key":"75178_CR40","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3389\/fnins.2015.00235","volume":"9","author":"MJ Bertoldo","year":"2015","unstructured":"Bertoldo, M. J., Faure, M., Dupont, J. & Froment, P. AMPK: A master energy regulator for gonadal function. Front. Neurosci. 9, 235 (2015).","journal-title":"Front. Neurosci."},{"key":"75178_CR41","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399411002109","volume":"14","author":"SM Schultze","year":"2012","unstructured":"Schultze, S. M., Hemmings, B. A., Niessen, M. & Tschopp, O. PI3K\/AKT, MAPK and AMPK signalling: Protein kinases in glucose homeostasis. Expert Rev. Mol. Med. 14, e1 (2012).","journal-title":"Expert Rev. Mol. Med."},{"key":"75178_CR42","doi-asserted-by":"crossref","unstructured":"Wang, S. et al. lncRNA Linc00173 modulates glucosemetabolism and multidrug chemoresistancein SCLC: Potential molecular panel for targeted therapy. Mol. Ther. (2021).","DOI":"10.1016\/j.ymthe.2021.11.003"},{"key":"75178_CR43","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1038\/s41598-022-08423-6","volume":"12","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y., Pan, S., Li, Y. & Wu, X. Exosomal miR-143-3p derived from follicular fluid promotes granulosa cell apoptosis by targeting BMPR1A in polycystic ovary syndrome. Sci Rep. 12, 4359 (2022).","journal-title":"Sci Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75178-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75178-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75178-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T05:17:13Z","timestamp":1729747033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75178-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,20]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["75178"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-75178-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,20]]},"assertion":[{"value":"13 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the Clinical Ethics Review Board of the Fourth Hospital of Shijiazhuang (Hebei, China), ethical approval number: 20220112.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declaration"}}],"article-number":"24636"}}