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However, the relationship between BAP31 and chemoresistance is uncertain. This study investigated the role of BAP31 in regulating the doxorubicin (Dox) resistance of hepatocellular carcinoma (HCC). The expression of proteins was assessed by Western blotting. The correlation between BAP31 expression and Dox resistance was examined by MTT and colony formation assays. Apoptosis was analyzed by flow cytometry and TdT-mediated dUTP nick end labeling assays. Western blot and immunofluorescence analyses were performed in the knockdown cell lines to explore the possible mechanisms. In this study, BAP31 was strongly expressed, and knockdown of BAP31 increased Dox chemosensitivity in cancer cells. Furthermore, the expression of BAP31 was higher in the Dox-resistant HCC cells than that in their parental cells; knockdown of BAP31 reduced the half maximal inhibitory concentration value and overcame Dox resistance in Dox-resistant HCC cells. In HCC cells, knockdown of BAP31 increased Dox-induced apoptosis and enhanced Dox chemosensitivity in vitro and in vivo. The potential mechanism by which BAP31 increased Dox-induced apoptosis is that BAP31 inhibited survivin expression by promoting FoxO1 nucleus\u2013cytoplasm translocation. Knockdown of BAP31 and survivin had a synergistic effect on Dox chemosensitivity by enhancing the apoptosis of HCC cells. These findings reveal that BAP31 knockdown enhances Dox chemosensitivity through the downregulation of survivin, suggesting that BAP31 is a potential therapeutic target for improving the treatment response of HCC with resistance to Dox.<\/jats:p>","DOI":"10.3390\/ijms24087622","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T03:01:48Z","timestamp":1682046108000},"page":"7622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Knockdown of BAP31 Overcomes Hepatocellular Carcinoma Doxorubicin Resistance through Downregulation of Survivin"],"prefix":"10.3390","volume":"24","author":[{"given":"Jingjing","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changli","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour heterogeneity and resistance to cancer therapies","volume":"15","author":"Shaw","year":"2018","journal-title":"Nat. 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