Down-regulation of UBC9 increases the sensitivity of hepatocellular carcinoma to doxorubicin
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Sufen Fang2,*, Junyao Qiu2,*, Zheng Wu2, Tao Bai2 and Wuhua Guo1
1Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China
2Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
*These authors have contributed equally to this work
Wuhua Guo, email: firstname.lastname@example.org
Keywords: UBC9, SUMOylation, hepatocellular carcinoma (HCC), doxorubicin (DOX), apoptosis
Received: December 20, 2016 Accepted: May 05, 2017 Published: May 17, 2017
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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