{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:44:30Z","timestamp":1753868670281,"version":"3.41.2"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002842"],"award-info":[{"award-number":["82002842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ring finger protein 135 (RNF135) is an E3 ubiquitin ligase that has been implicated in the tumorigenesis of multiple human malignancies. However, whether RNF135 plays a role in the development of human osteosarcoma (OS) remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNF135 expression in 20 human OS and 20 human osteochondroma specimens were evaluated by means of immunohistochemistry staining. The effects of shRNA\u2010mediated RNF135 knockdown on human OS cell growth and apoptosis were evaluated through a panel of in vitro studies on cell proliferation, colony formation, exposure of phosphatidylserine on the cell surface, and caspase 3\/7 activation. The protein levels of PI3K, AKT, and p\u2010AKT were determined by western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected significantly higher RNF135 levels in human OS tissues than human osteochondroma tissues. In in vitro studies, shRNA\u2010mediated RNF135 knockdown in human OS cells inhibited proliferation and induced apoptosis. In addition, RNF135 knockdown reduced PI3K and p\u2010AKT protein levels and activated caspase 3 and 7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results supported that RNF135 contributes to human OS development through PI3K\/AKT\u2010dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.2159","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T04:41:03Z","timestamp":1723178463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RNF135<\/scp> Promotes Human Osteosarcoma Cell Growth and Inhibits Apoptosis by Upregulating the <scp>PI3K<\/scp>\/<scp>AKT<\/scp> Pathway"],"prefix":"10.1002","volume":"7","author":[{"given":"Bingyao","family":"Chen","sequence":"first","affiliation":[{"name":"Second Department of Orthopedics Beijing Daxing District People's Hospital  Beijing China"},{"name":"Department of Orthopedics Aerospace Central Hospital  Beijing China"},{"name":"Senior Department of Orthopedics The Fourth Medical Center of PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinglong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopedics The Fourth Medical Center of PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangze","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Aerospace Central Hospital  Beijing China"},{"name":"Senior Department of Orthopedics The Fourth Medical Center of PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-5987","authenticated-orcid":false,"given":"Xing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Aerospace Central Hospital  Beijing China"},{"name":"Senior Department of Orthopedics The Fourth Medical Center of PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_11_2_1","DOI":"10.1080\/14737140.2018.1413939"},{"issue":"12","key":"e_1_2_11_3_1","first-page":"547","article-title":"Osteosarcoma: A Meta\u2010Analysis and Review of the Literature","volume":"44","author":"Friebele J. C.","year":"2015","journal-title":"American Journal of Orthopedics"},{"doi-asserted-by":"publisher","key":"e_1_2_11_4_1","DOI":"10.1016\/j.ctrv.2013.11.006"},{"doi-asserted-by":"publisher","key":"e_1_2_11_5_1","DOI":"10.1007\/s11914-023-00803-9"},{"issue":"1","key":"e_1_2_11_6_1","article-title":"The Targeted Therapies for Osteosarcoma via Six Major Pathways","volume":"17","author":"Wang S.","year":"2024","journal-title":"Current Molecular Pharmacology"},{"doi-asserted-by":"publisher","key":"e_1_2_11_7_1","DOI":"10.1038\/s41418-020-00703-w"},{"doi-asserted-by":"publisher","key":"e_1_2_11_8_1","DOI":"10.1186\/s12943-020-01262-x"},{"doi-asserted-by":"publisher","key":"e_1_2_11_9_1","DOI":"10.1007\/s12032-014-0093-6"},{"doi-asserted-by":"publisher","key":"e_1_2_11_10_1","DOI":"10.1016\/S1044-579X(02)00095-0"},{"doi-asserted-by":"publisher","key":"e_1_2_11_11_1","DOI":"10.2174\/138161209789271825"},{"doi-asserted-by":"publisher","key":"e_1_2_11_12_1","DOI":"10.1074\/jbc.M804259200"},{"issue":"23","key":"e_1_2_11_13_1","first-page":"9758","article-title":"A pan\u2010Cancer Analysis of Ring Finger Protein 135 and Its Relationship to Triple\u2010Negative Breast Cancer Proliferation and Metastasis","volume":"14","author":"Yao Y.","year":"2022","journal-title":"Aging"},{"doi-asserted-by":"publisher","key":"e_1_2_11_14_1","DOI":"10.1002\/cam4.832"},{"doi-asserted-by":"publisher","key":"e_1_2_11_15_1","DOI":"10.2478\/bjmg-2020-0002"},{"doi-asserted-by":"publisher","key":"e_1_2_11_16_1","DOI":"10.1038\/srep20642"},{"doi-asserted-by":"publisher","key":"e_1_2_11_17_1","DOI":"10.3389\/fonc.2021.752511"},{"doi-asserted-by":"publisher","key":"e_1_2_11_18_1","DOI":"10.1016\/j.canlet.2014.11.034"},{"doi-asserted-by":"publisher","key":"e_1_2_11_19_1","DOI":"10.1186\/s12957-019-1566-z"},{"doi-asserted-by":"publisher","key":"e_1_2_11_20_1","DOI":"10.1126\/science.1115035"},{"doi-asserted-by":"publisher","key":"e_1_2_11_21_1","DOI":"10.3389\/fonc.2022.1072701"},{"doi-asserted-by":"publisher","key":"e_1_2_11_22_1","DOI":"10.3390\/ijms21041309"},{"doi-asserted-by":"publisher","key":"e_1_2_11_23_1","DOI":"10.3892\/or.2020.7813"},{"doi-asserted-by":"publisher","key":"e_1_2_11_24_1","DOI":"10.1155\/2019\/9612125"},{"doi-asserted-by":"publisher","key":"e_1_2_11_25_1","DOI":"10.3727\/096504020X15868639303417"},{"doi-asserted-by":"publisher","key":"e_1_2_11_26_1","DOI":"10.1016\/j.ebiom.2020.102955"},{"doi-asserted-by":"publisher","key":"e_1_2_11_27_1","DOI":"10.1146\/annurev-biochem-090120-013613"},{"doi-asserted-by":"publisher","key":"e_1_2_11_28_1","DOI":"10.1016\/j.omtn.2017.12.010"},{"issue":"9","key":"e_1_2_11_29_1","first-page":"1857","article-title":"Small Molecule TSC01682 Inhibits Osteosarcoma Cell Growth by Specifically Disrupting the CUL4B\u2010DDB1 Interaction and Decreasing the Ubiquitination of CRL4B E3 Ligase Substrates","volume":"9","author":"Chen B.","year":"2019","journal-title":"American Journal of Cancer Research"},{"doi-asserted-by":"publisher","key":"e_1_2_11_30_1","DOI":"10.1155\/2020\/8450606"},{"doi-asserted-by":"publisher","key":"e_1_2_11_31_1","DOI":"10.1080\/15384101.2023.2205201"},{"doi-asserted-by":"publisher","key":"e_1_2_11_32_1","DOI":"10.3390\/molecules26061499"},{"doi-asserted-by":"publisher","key":"e_1_2_11_33_1","DOI":"10.1371\/journal.pone.0184969"},{"issue":"1","key":"e_1_2_11_34_1","first-page":"475","article-title":"Downregulation of miR\u2010485\u20103p Promotes Glioblastoma Cell Proliferation and Migration via Targeting RNF135","volume":"18","author":"Zhang Y.","year":"2019","journal-title":"Experimental and Therapeutic Medicine"},{"doi-asserted-by":"publisher","key":"e_1_2_11_35_1","DOI":"10.2119\/molmed.2010.00079"},{"doi-asserted-by":"publisher","key":"e_1_2_11_36_1","DOI":"10.1186\/s40164-022-00363-1"},{"doi-asserted-by":"publisher","key":"e_1_2_11_37_1","DOI":"10.1038\/nm.3915"},{"doi-asserted-by":"publisher","key":"e_1_2_11_38_1","DOI":"10.1016\/j.yexmp.2022.104787"},{"doi-asserted-by":"publisher","key":"e_1_2_11_39_1","DOI":"10.3389\/fonc.2023.1124600"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.2159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T02:56:28Z","timestamp":1724813788000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.2159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":38,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/cnr2.2159"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.2159","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"type":"print","value":"2573-8348"},{"type":"electronic","value":"2573-8348"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2024-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2159"}}