{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:56:53Z","timestamp":1778738213027,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001026","name":"National Breast Cancer Foundation","doi-asserted-by":"publisher","award":["IIRS-18-103"],"award-info":[{"award-number":["IIRS-18-103"]}],"id":[{"id":"10.13039\/501100001026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["T 1062 Firnberg Program"],"award-info":[{"award-number":["T 1062 Firnberg Program"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein that has been shown to regulate proliferation, invasion and metastasis in a variety of cancer types. We previously demonstrated that YB-1 is overexpressed in mesothelioma cells and its knockdown significantly reduces tumour cell proliferation, migration, and invasion. However, the mechanisms driving these effects are unclear. Here, we utilised an unbiased RNA-seq approach to characterise the changes to gene expression caused by loss of YB-1 knockdown in three mesothelioma cell lines (MSTO-211H, VMC23 and REN cells). Bioinformatic analysis showed that YB-1 knockdown regulated 150 common genes that were enriched for regulators of mitosis, integrins and extracellular matrix organisation. However, each cell line also displayed unique gene expression signatures, that were differentially enriched for cell death or cell cycle control. Interestingly, deregulation of STAT3 and p53-pathways were a key differential between each cell line. Using flow cytometry, apoptosis assays and single-cell time-lapse imaging, we confirmed that MSTO-211H, VMC23 and REN cells underwent either increased cell death, G1 arrest or aberrant mitotic division, respectively. In conclusion, this data indicates that YB-1 knockdown affects a core set of genes in mesothelioma cells. Loss of YB-1 causes a cascade of events that leads to reduced mesothelioma proliferation, dependent on the underlying functionality of the STAT3\/p53-pathways and the genetic landscape of the cell.<\/jats:p>","DOI":"10.3390\/cancers12082285","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T08:28:35Z","timestamp":1597393715000},"page":"2285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms"],"prefix":"10.3390","volume":"12","author":[{"given":"Thomas G.","family":"Johnson","sequence":"first","affiliation":[{"name":"The Asbestos Diseases Research Institute (ADRI), Concord Hospital, Concord, Sydney 2139, Australia"},{"name":"The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney 2139, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney Concord Clinical School, Sydney 2139, Australia"},{"name":"Sydney Catalyst Translational Research Centre, Sydney 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Schelch","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-9352","authenticated-orcid":false,"given":"Kaitao","family":"Lai","sequence":"additional","affiliation":[{"name":"The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney 2139, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney Concord Clinical School, Sydney 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila A.","family":"Marzec","sequence":"additional","affiliation":[{"name":"The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Kennerson","sequence":"additional","affiliation":[{"name":"The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney 2139, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney Concord Clinical School, Sydney 2139, Australia"},{"name":"Molecular Medicine Laboratory, Concord Repatriation General Hospital, Sydney 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-9340","authenticated-orcid":false,"given":"Michael","family":"Grusch","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-5223","authenticated-orcid":false,"given":"Glen","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Otago, Dunedin 9054, New Zealand"},{"name":"The Maurice Wilkins Centre, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-9226","authenticated-orcid":false,"given":"Andrew","family":"Burgess","sequence":"additional","affiliation":[{"name":"The ANZAC Research Institute, Concord Repatriation General Hospital, Sydney 2139, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney Concord Clinical School, Sydney 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"ref_1","unstructured":"Australian Institute of Health & Welfare (2020, July 20). 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