USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt
USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt
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USP22 敲低通过上调 Smad4 和抑制 Akt 增强肝细胞癌细胞对 5-Fu 的化疗敏感性
DOI：
10.18632/oncotarget.15798
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Rongkuan Li
中科院分区：
文献类型：
--
作者：
Jing Zhang;Nan Luo;Yu Tian;Jiazhi Li;Xiaozhou Yang;Huimin Yin;Congshu Xiao;Jie Sheng;Yang Li;Bo Tang;Rongkuan Li
USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy. Silencing USP22 in chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in vitro; suppressed tumorigenic and metastatic capacities in vivo; and inhibited drug resistance-related proteins (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its function through down-regulating PI3K and activating Smad4, which inhibited phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells. Our results, for the first time, provide evidence that USP22 plays a critical role in the development of chemoresistant HCC cells and that high USP22 expression serves as a molecular marker for the prognosis of HCC patients who undergo chemotherapy.
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影响因子：
4.3
作者：
Zhang, Xiao-Yong;Pfeiffer, Harla K.;McMahon, Steven B.
通讯作者：
McMahon, Steven B.
影响因子：
81.5
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
通讯作者：
Gores, Gregory
影响因子：
5.1
作者：
Marrero, Jorge A;Pelletier, Shawn
通讯作者：
Pelletier, Shawn
影响因子：
1.5
作者：
Gilles, HoChong;Garbutt, Tonora;Landrum, Jasmine
通讯作者：
Landrum, Jasmine
DOI：
10.1016/s0015-6264(78)80335-6
发表时间：
1986
期刊：
The New Zealand medical journal
影响因子：
--
作者：
D. Woodfield
通讯作者：
D. Woodfield