title: Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-κB activation.
abstract: Hepatocellular carcinoma is the most common type of liver cancer. Radiotherapy combined with chemotherapy is the treatment of choice for hepatocellular carcinoma, but radioresistance of the cancer remains a significant therapeutic hindrance. Here, we provided several lines of evidence that small ubiquitin-like modifier (SUMO)-specific protease 6 (SENP6) could be an attractive molecular target for the treatment of hepatocellular carcinoma. By using immunohistochemical and real-time PCR, we showed that SENP6 was overexpressed in more than half of the hepatocellular carcinoma tissues. The growth retardation and radiosensitization were caused by silencing of SENP6 in the hepatocellular carcinoma cell lines using lentiviral shRNA. Moreover, SENP6 was required for radiation-induced NF-κB activation and the half-life of IκBα, a well-known inhibitor of NF-κB, and was extended by SENP6 silencing. Thus, our data demonstrated that SENP6 is an attractive drug target for anticancer therapy and radiosensitization.
authors: Department of Medical Oncology, Changzheng Hospital, Shanghai 200070, China. Jianxinqiancz@hotmail.com
authors: Jianxin
authors: J
authors: Qian
authors: Yizhou
authors: Y
authors: Luo
authors: Xiaoqiang
authors: X
authors: Gu
authors: Xi
authors: X
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human