Down-regulation of UBC9 increases the sensitivity of hepatocellular carcinoma to doxorubicin.
Down-regulation of UBC9 increases the sensitivity of hepatocellular carcinoma to doxorubicin.
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UBC9的下调增加了肝细胞癌对阿霉素的敏感性。
DOI：
10.18632/oncotarget.17939
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Guo W
中科院分区：
文献类型：
--
作者：
Fang S;Qiu J;Wu Z;Bai T;Guo W
UBC 9是SUMO化所需的E2-缀合酶，并参与调节几种关键的细胞途径。UBC 9在某些肿瘤中过表达，如肺腺癌、卵巢癌和黑色素瘤，这意味着它具有特殊的临床意义。然而，UBC 9在肝细胞癌（HCC）药物反应性中的作用尚不清楚。本研究旨在探讨UBC 9在肝癌中的临床病理学意义以及UBC 9介导肝癌细胞对阿霉素（DOX）化疗敏感性的机制。我们发现，相对于邻近的正常组织，UBC 9在HCC中显著过表达，这与肿瘤大小、肿瘤微卫星形成和肿瘤包膜密切相关。我们的研究结果还表明，通过shRNA下调UBC 9降低了Bcl-2和Bcl-xl的表达，并增加了促凋亡蛋白切割的Caspase 3的表达。这些变化与DOX引起的细胞凋亡减少有关。此外，我们观察到一个机制，涉及P38和ERK 1/2信号通路的调制。总之，我们的研究结果表明，下调UBC 9使细胞对抗癌药物敏感，可能与ERK 1/2和P38活化的调节有关，并与内在凋亡途径相互作用。因此，UBC 9的敲低可能具有肿瘤抑制作用，并且UBC 9可能是治疗HCC癌症的潜在靶点。
UBC9 is an E2-conjugating enzyme that is required for SUMOylation and has been implicated in regulating several critical cellular pathways. UBC9 is overexpressed in certain tumors, such as lung adenocarcinoma, ovarian carcinoma and melanoma, which implies that it has special clinical significance. However, the role of UBC9 in Hepatocellular carcinoma (HCC) drug responsiveness is not clear. In this study, we investigated the clinicopathological significance of UBC9 in HCC and investigated the mechanism of UBC9-mediated chemosensitivity to doxorubicin (DOX) in hepatocellular carcinoma cells. We found that relative to adjacent normal tissues, UBC9 was markedly overexpressed in HCC, which closely correlated with tumor size, tumor microsatellite formation, and tumor encapsulation. Our results also showed that down-regulation of UBC9 by shRNA reduced the expression of Bcl-2 and Bcl-xl and increased the expression of cleaved-Caspase3, which is a proapoptotic protein. These changes were associated with reduced apoptosis in response to DOX. Furthermore, we observed a mechanism involving modulation of the P38 and ERK1/2 signaling pathways. Together, our results indicate that down-regulation of UBC9 sensitizes cells to anticancer drugs, is possibly associated with the regulation of ERK1/2 and P38 activation and interacts with the intrinsic apoptosis pathway. Thus, knockdown of UBC9 may have a tumor suppressor effect and UBC9 could be a potential target for the treatment of HCC cancer.
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影响因子：
2.6
作者：
Lencioni R;Kudo M;Ye SL;Bronowicki JP;Chen XP;Dagher L;Furuse J;Geschwind JF;de Guevara LL;Papandreou C;Takayama T;Yoon SK;Nakajima K;Lehr R;Heldner S;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
6.7
作者：
Cho, Ju-Yeon;Paik, Yong-Han;Yoo, Byung Chul
通讯作者：
Yoo, Byung Chul
影响因子：
2.8
作者：
Han, Ji-Youn;Lee, Geon Kook;Lee, Jin Soo
通讯作者：
Lee, Jin Soo
Ubc9 与核定位信号相互作用并介导成对同源染色体蛋白 Vsx-1 的核定位，与 SUMO-1 修饰无关
DOI：
10.1073/pnas.101129698
发表时间：
2001-05-08
影响因子：
11.1
作者：
Kurtzman, AL;Schechter, N
通讯作者：
Schechter, N
DOI：
10.1111/j.1440-1681.2007.04593.x
发表时间：
2007-05-01
影响因子：
2.9
作者：
Lei, Xiao-Yong;Zhong, Miao;Liao, Duan-Fang
通讯作者：
Liao, Duan-Fang