{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:50:53Z","timestamp":1785336653868,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"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":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in lung adenocarcinoma (LUAD) are still unclear. Herein, we investigated the level of RNF135 in tumor tissues of LUAD patients using the UALCAN database and confirmed the data by real\u2010time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration\/invasion capability of LUAD cells were investigated by sphere formation, flow cytometry, wound healing, and transwell assay. Limiting dilution xenograft assay and intracardiac injection of LUAD cells were applied to assess the implications of RNF135 in tumorigenesis and brain metastasis. Our results revealed that RNF135 was upregulated in tumor tissues of LUAD patients and was positively correlated with poor prognosis. Knockdown of RNF135 suppressed cancer stem cells (CSCs)\u2010like properties, and migration\/invasion capability of A549 and NCI\u2010H1975 cells. Conversely, overexpression of RNF135 augmented CSCs\u2010like traits and migration\/invasion ability of LUAD cells. Limiting dilution xenograft assay demonstrated that RNF135 was required for the self\u2010renewal of CSCs to initiate LUAD development. Overexpression of RNF135 in A549 cells increased their ability to metastasize to the brain in vivo. Mechanistically, the transcriptional activation of RNF135 by LSD1 involved H3K9me2 demethylation at the promoter region of RNF135. Reexpression of RNF135 in LSD1\u2010silenced A549 cells was able to reverse LSD1\u2010mediated stemness maintenance and migration\/invasion capability. Overall, our results implied that targeting of LSD1\/RNF135 axis might be a feasible method to suppress tumorigenesis and brain metastasis of LUAD patients.<\/jats:p>","DOI":"10.1002\/tox.24407","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T08:35:40Z","timestamp":1725093340000},"page":"5321-5333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epigenetic Regulation of <scp>RNF135<\/scp> by <scp>LSD1<\/scp> Promotes Stemness Maintenance and Brain Metastasis in Lung\u00a0Adenocarcinoma"],"prefix":"10.1002","volume":"39","author":[{"given":"Xiaohan","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery The First Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjian","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-3596","authenticated-orcid":false,"given":"Liming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/1516\u20103180.2020.0763.16022021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.043"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijc.IJC_51_21"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66788"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010021\u201002028\u20105"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804259200"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12104\u2010019\u201009895\u2010w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204429"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20642"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2023.102282"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.832"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.752511"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.15586\/aei.v52i2.1048"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2022.11.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.07.015"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.012"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04020"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201006\u20101570"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201008\u20101735"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp324"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25349"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417\u2010021\u201000297\u20106"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.mcr\u201017\u20100637"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.09.018"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.12382"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2499"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.02.006"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010021\u201001107\u20104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.001"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.225334.113"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208927"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.027"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.038"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1546"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1147674"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.353"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.24407","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T09:37:08Z","timestamp":1731663428000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.24407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,31]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/tox.24407"],"URL":"https:\/\/doi.org\/10.1002\/tox.24407","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,31]]},"assertion":[{"value":"2024-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}