Knockdown of BAP31 Overcomes Hepatocellular Carcinoma Doxorubicin Resistance through Downregulation of Survivin.
Knockdown of BAP31 Overcomes Hepatocellular Carcinoma Doxorubicin Resistance through Downregulation of Survivin.
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DOI：
10.3390/ijms24087622
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发表时间：
2023-04-21
影响因子：
5.6
通讯作者：
Wang, Bing
中科院分区：
文献类型：
--
作者：
Liu, Jingjing;Zhang, Qi;Wang, Changli;Yang, Jiaying;Yang, Sheng;Wang, Tianyi;Wang, Bing
B细胞受体相关蛋白31（BAP 31）的表达在许多肿瘤类型中增加，并且据报道参与增殖、迁移和凋亡。然而，BAP 31与化疗耐药性之间的关系尚不确定。本研究旨在探讨BAP31在调节肝细胞癌（HCC）多柔比星（Dox）耐药中的作用。Western blotting检测蛋白表达。MTT法和集落形成实验检测BAP 31表达与阿霉素耐药的相关性。通过流式细胞术和TdT介导的dUTP缺口末端标记法分析细胞凋亡。通过Western blot和免疫荧光分析，探讨了其可能的作用机制。在这项研究中，BAP31被强烈表达，并且BAP31的敲低增加了癌细胞中的Dox化疗敏感性。BAP31在Dox耐药肝癌细胞中的表达高于其亲本细胞，敲低BAP31可降低Dox耐药肝癌细胞的半数抑制浓度，克服Dox耐药。在肝癌细胞中，BAP 31的敲低增加了Dox诱导的凋亡，并增强了体内外Dox化疗敏感性。BAP 31增加Dox诱导的细胞凋亡的可能机制是通过促进FoxO1核质易位抑制survivin的表达。BAP31和Survivin的敲低通过促进HCC细胞的凋亡而对Dox化疗敏感性具有协同作用。这些发现揭示BAP31敲低通过下调生存素增强Dox化疗敏感性，表明BAP31是改善对Dox耐药的HCC的治疗反应的潜在治疗靶点。
The expression of B-cell receptor associated protein 31 (BAP31) is increased in many tumor types, and it is reported to participate in proliferation, migration, and apoptosis. 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–cytoplasm 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.
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影响因子：
3.9
作者：
Quistgaard, Esben M.
通讯作者：
Quistgaard, Esben M.
影响因子：
5
作者：
Liu T;Yu J;Ge C;Zhao F;Miao C;Jin W;Su Y;Geng Q;Chen T;Xie H;Cui Y;Yao M;Li J;Hou H;Li H
通讯作者：
Li H
影响因子：
2.7
作者：
Liang, Haiyan;Dong, Jiqiao;Ling, Bin
通讯作者：
Ling, Bin
影响因子：
9.7
作者：
Altieri, Dario C.
通讯作者：
Altieri, Dario C.
BAP31 是一种新定义的癌症/睾丸抗原，调节增殖、迁移和侵袭以促进宫颈癌进展。
影响因子：
9
作者：
Dang E;Yang S;Song C;Jiang D;Li Z;Fan W;Sun Y;Tao L;Wang J;Liu T;Zhang C;Jin B;Wang J;Yang K
通讯作者：
Yang K