{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T20:54:26Z","timestamp":1772830466478,"version":"3.50.1"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J\ufffdCell Death"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:p> Patients with chronic hepatitis C virus (HCV) infection risk complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Previously, our proteomic examination of hepatocytes carrying a HCV-replicon revealed that deregulation of cytoskeletal dynamics may be a potential mechanism of viral-induced HCC growth. Here, we demonstrate the effect of HCV replication on the microtubule regulator stathmin (STMN1) in HCC cells. We further explore how the altered activity or synthesis of stathmin affects cellular proliferation and sensitivity to apoptosis in control HCC cells (Huh7.5) and experimental HCV-replicon harboring HCC cells (R-Huh7.5). The HCV-replicon harboring HCC cells (R-Huh 7.5) lack viral structural genes\/proteins for acute infectivity and thus is the standard model for in vitro chronic infection study. Knockdown of endogenous stathmin reduced sensitivity to apoptosis in replicon cells. Meanwhile, constitutively active stathmin increased sensitivity to apoptosis in replicon cells. In addition, overexpression of constitutively active stathmin reduced cell proliferation in both control and replicon cells. These findings implicate, for the first time, a novel role for stathmin in viral replication\u2013related apoptosis. Stathmin\u2019s potential role in HCV replication and HCC make it a candidate for the future study of viral-induced malignancies. <\/jats:p>","DOI":"10.1177\/1179066018785141","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T11:27:53Z","timestamp":1530703673000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Oncoprotein Stathmin Modulates Sensitivity to Apoptosis in Hepatocellular Carcinoma Cells During Hepatitis C Viral Replication"],"prefix":"10.1177","volume":"11","author":[{"given":"Nu T","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"},{"name":"Department of Hematology and Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie M","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darshil","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Q","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chae Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronik","family":"Khachatoorian","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikita","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara E","family":"Magyar","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekambaram","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaithilingaraja","family":"Arumugaswami","sequence":"additional","affiliation":[{"name":"Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"},{"name":"Department of Surgery and Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asim","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel Wheeler","family":"French","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA"},{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"bibr1-1179066018785141","doi-asserted-by":"crossref","unstructured":"Messina P, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61:77\u201387.","DOI":"10.1002\/hep.27259"},{"key":"bibr2-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27095"},{"key":"bibr3-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-939841"},{"key":"bibr4-1179066018785141","first-page":"339","volume":"13","author":"Lu NT","year":"2016","journal-title":"Cancer Genomics Proteomics"},{"key":"bibr5-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2004.00196.x"},{"key":"bibr6-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27453"},{"key":"bibr7-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201504"},{"key":"bibr8-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.124"},{"key":"bibr9-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-3215-z"},{"key":"bibr10-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20627"},{"key":"bibr11-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.639625"},{"key":"bibr12-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26496"},{"key":"bibr13-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500125R"},{"key":"bibr14-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.04.011"},{"key":"bibr15-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2014.127"},{"key":"bibr16-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.018"},{"key":"bibr17-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.13001-13014.2002"},{"key":"bibr18-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000182"},{"key":"bibr19-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.002"},{"key":"bibr20-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.75"},{"key":"bibr21-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510662200"},{"key":"bibr22-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235583100"},{"key":"bibr23-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030017"},{"key":"bibr24-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06923-11"},{"key":"bibr25-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111605200"},{"key":"bibr26-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101466200"},{"key":"bibr27-1179066018785141","first-page":"299","volume":"69","author":"Mistry SJ","year":"2002","journal-title":"Mt Sinai J Med"},{"key":"bibr28-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20187"},{"key":"bibr29-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-1013"},{"key":"bibr30-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-7-1547"},{"key":"bibr31-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2007.00429.x"},{"key":"bibr32-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.044420"},{"key":"bibr33-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3413"},{"key":"bibr34-1179066018785141","first-page":"29001","volume-title":"c-Jun N-terminal kinase phosphorylation of stathmin confers protection against cellular stress","volume":"285","author":"Ng DC","year":"2010"},{"key":"bibr35-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025513106330"},{"key":"bibr36-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61101-7"},{"key":"bibr37-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-30-87"},{"key":"bibr38-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-011-0728-4"},{"key":"bibr39-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26406"},{"key":"bibr40-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X13515825"},{"key":"bibr41-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.06.002"},{"key":"bibr42-1179066018785141","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516879113"}],"container-title":["Journal of Cell Death"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1179066018785141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1179066018785141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1179066018785141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T21:29:00Z","timestamp":1728509340000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1179066018785141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,1]]},"references-count":42,"alternative-id":["10.1177\/1179066018785141"],"URL":"https:\/\/doi.org\/10.1177\/1179066018785141","relation":{},"ISSN":["1179-0660","1179-0660"],"issn-type":[{"value":"1179-0660","type":"print"},{"value":"1179-0660","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,1]]},"article-number":"1179066018785141"}}