Journal
BIOTECHNOLOGY LETTERS
Volume 35, Issue 1, Pages 29-37Publisher
SPRINGER
DOI: 10.1007/s10529-012-1048-7
Keywords
Hepatitis B virus; Hepatocellular carcinoma; Inhibitor Bcl-2; Inhibitor P16; Notch; shRNA
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Funding
- National Science Foundation of China [30971352]
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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.
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