{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:20:11Z","timestamp":1781706011186,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hypoxia is a common phenomenon for solid tumors due to a lack of effective vascular system, and has been deemed as an important factor that drives the progression of thyroid cancer (TC) via altering the characteristics of tumor cells. The present study suggested that hypoxic TC cells enhanced cancer stem cell properties and progression of TC by delivering long intergenic non\u2010protein coding RNA 665 (LINC00665)\u2010containing exosomes. Specifically, TPC1 cells were exposed to normoxic or hypoxic environment, and it was found that hypoxic TPC1 cells\u2010secreted exosomes (H\u2010exo) were enriched with LINC00665, compared to normoxic TPC1 cells\u2010derived exosomes (N\u2010exo). In addition, by establishing the in vitro exosomes\u2010TC cells coculture system, we found that in contrast to N\u2010exo, H\u2010exo apparently promoted cell proliferation, epithelial mesenchymal transition (EMT) and cancer stem cell properties via delivering LINC00665. This was supported by the in vivo results that H\u2010exo transferred LINC00665 to promote tumorigenesis and the expression of EMT and stemness\u2010associated markers in xenograft tumor\u2010bearing mice models. Further mechanical experiments validated that LINC00665 combined with EPHB4 mRNA to sustain its stability to enhance cancer aggressiveness of TC. Altogether, our findings verified that hypoxic TC cells\u2010secreted exosomes regulated the LINC00665\/EPHB4 axis to enhance cancer stem cell properties of TC, providing novel signatures for TC diagnosis and therapy.<\/jats:p>","DOI":"10.1002\/cbin.12274","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T11:05:31Z","timestamp":1737371131000},"page":"384-396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hypoxic Cancer Cells\u2010Derived Exosomes Strengthen the Development of Cancer Stem Cell\u2010Like Properties Through Delivering LINC00665 in Thyroid Cancer Cells"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6280-5795","authenticated-orcid":false,"given":"Ming","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Thyroid Vascular Surgery, Jingzhou Central Hospital Jingzhou Hospital Affiliated to Yangtze University Jingzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery Huanggang Central Hospital, Huangzhou District Huanggang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jingzhou Central Hospital Jingzhou Hospital Affiliated to Yangtze University Jingzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchu","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Thyroid Vascular Surgery, Jingzhou Central Hospital Jingzhou Hospital Affiliated to Yangtze University Jingzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.111671"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.933329"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.10.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486422"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S327621"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0322"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.12.057"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01655-6"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.37455"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.792046"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-022-00343-7"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0509"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/cej.0000000000000346"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86767"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.05.018"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603642"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1913"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02147-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2021.5284"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.13286"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00656-0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03346-4"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2016.03.011"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac548"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00114"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-022-01801-0"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9510"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.4103\/njms.NJMS_60_17"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2018.06.006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31092"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01690-z"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04303-5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.07.001"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01280"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24678"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12351"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-023-00657-4"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2023.110596"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.12659\/msm.907389"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci159839"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1530\/erc-19-0008"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2022.113268"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23072"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29252"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-023-00356-y"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.66142"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0959-5"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0120-1"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202003_20674"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.12274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:53:35Z","timestamp":1741730015000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.12274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/cbin.12274"],"URL":"https:\/\/doi.org\/10.1002\/cbin.12274","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]},"assertion":[{"value":"2024-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}