Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells

被引:23
作者
Wang, Fan [1 ]
Xia, Xiumei [1 ]
Wang, Jinling [1 ]
Sun, Qian [1 ]
Luo, Jin [1 ]
Cheng, Bin [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Gastroenterol & Hepatol, Tongji Med Coll, Wuhan 430030, Peoples R China
基金
美国国家科学基金会;
关键词
Hepatitis B virus; Hepatocellular carcinoma; Inhibitor Bcl-2; Inhibitor P16; Notch; shRNA; HEPATOCELLULAR-CARCINOMA; TUMOR SUPPRESSION; HUMAN LIVER; CANCER; GENE; IDENTIFICATION; EXPRESSION; SURVIVAL; HOMOLOG; PATHWAY;
D O I
10.1007/s10529-012-1048-7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Hepatocellular carcinoma (HCC) is a malignant tumor and hepatitis B virus X protein (HBx) plays a crucial role in its pathogenesis. The Notch1 signaling pathway is involved in various malignant tumors including liver cancers and down-regulation of Notch-1 may exert anti-tumor effects. Here, we demonstrate that inhibition of Notch1 by plasmid-based shRNA suppresses growth of human hepatic cells transfected with HBx through G0/G1 cell cycle arrest and apoptosis inhibition, possibly linked to the promoted expression of cyclin-dependent kinase inhibitor, P16, and decreased expression of apoptosis inhibitor, Bcl-2. The anti-proliferative and pro-apoptotic effects of Notch1 shRNA in HBx-transformed L02 cell may be partly mediated by down-regulation of nuclear factor-kappaB (NF-kappa B) binding activities, demonstrating possible cross-talk between Notch-1 and NF-kappa B signaling pathways. The oncogene HBx may therefore induce malignant transformation of human hepatic cells via Notch1 pathway, indicating that Notch1 plays a crucial role in HBx-related liver cancer and could be an effective therapeutic target for HCC.
引用
收藏
页码:29 / 37
页数:9
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