FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma.
FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma.
复制标题
DOI：
10.3389/fonc.2022.930220
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
Li, Jinjun
中科院分区：
文献类型：
--
作者：
Wang, Zhenyu;Chen, Xiaoxia;Zhou, Lianer;Zhao, Xinge;Ge, Chao;Zhao, Fangyu;Xie, Haiyang;Chen, Taoyang;Tian, Hua;Li, Hong;Li, Jinjun
关键词：
F-box蛋白对恶性肿瘤至关重要，因为它们控制着控制多种细胞过程的关键蛋白质的周转。F-box蛋白9（FBXO 9）属于F-box蛋白家族，在血液恶性肿瘤中表现出致癌特性。然而，FBXO 9在肝细胞癌（HCC）中的功能和分子机制尚不清楚。在这里，我们报告说，FBXO 9是显着过表达的HCC。功能丧失和获得实验表明，FBXO 9在体外和体内均促进HCC细胞增殖和转移。从机制上讲，FBXO 9作为直接上游转录因子，受锌指蛋白143（ZNF 143）调控，通过靶向F-box和WD重复结构域7（FBXW 7）进行泛素化和降解，加速肿瘤生长和转移。此外，我们发现FBXO 9敲减后，HCC细胞对乐伐替尼和索拉非尼治疗更敏感。综上所述，我们的研究结果表明，ZNF 143-FBXO 9-FBXW 7信号调节轴可能参与HCC的肿瘤进展，并表明FBXO 9可能是HCC的潜在生物标志物和治疗靶点。
F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mechanism of FBXO9 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that FBXO9 was remarkably overexpressed in HCC. Loss- and gain-of-function experiments showed that FBXO9 facilitates HCC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, as a direct upstream transcription factor, FBXO9 is regulated by zinc finger protein 143 (ZNF143) and accelerates tumor growth and metastasis by targeting the F-box and WD repeat domain containing 7 (FBXW7) for ubiquitination and degradation. Additionally, we found that with FBXO9 knockdown, HCC cells were more sensitive to treatment with lenvatinib and sorafenib. In summary, our results demonstrate that a ZNF143-FBXO9-FBXW7 signaling regulatory axis may be involved in tumor progression in HCC, and suggest that FBXO9 could be a potential biomarker and therapeutic target for HCC.
登录
查看更多内容
影响因子：
5.2
作者：
Hynes-Smith, R. Willow;Swenson, Samantha A.;Buckley, Shannon M.
通讯作者：
Buckley, Shannon M.
DOI：
10.1016/s1499-3872(14)60029-1
发表时间：
2014-04-15
影响因子：
3.3
作者：
Yu, Jun;Zhang, Wu;Zheng, Shu-Sen
通讯作者：
Zheng, Shu-Sen
FBXO22 降解核 PTEN 促进肿瘤发生
影响因子：
16.6
作者：
Ge, Meng-Kai;Zhang, Na;Shen, Shao-Ming
通讯作者：
Shen, Shao-Ming
环状 RNA hsa_circ_0001306 作为竞争性内源 RNA 通过海绵 miR-527 在肝细胞癌中调节 FBXW7 表达
影响因子：
3.9
作者：
Wu Y;Fan T;Zhao Y;Hu R;Yan D;Sun D;Gao L;Qin L;Xue X
通讯作者：
Xue X
影响因子：
3.7
作者：
El-mezayen, Hatem;Yamamura, Kensuke;Baba, Hideo
通讯作者：
Baba, Hideo