RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway.

Aberrant Notch signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell growth. However, the role of Notch signaling in HCC and its underlying mechanism remain elusive. RBP-J-interacting and tubulin-associated (RITA) mediates the nuclear export of RBP-J to tubulin fibers and downregulates Notch-mediated transcription. In this study, we found that RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Our findings indicate that RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC.

Wang H ，Yang Z ，Liu C ，Huang S ，Wang H ，Chen Y ，Chen G ... -  《-》

RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis.

Wang H ，Chen G ，Wang H ，Liu C ... -  《ONCOLOGY RESEARCH》

Recombinant human adenovirus-p53 injection induced apoptosis in hepatocellular carcinoma cell lines mediated by p53-Fbxw7 pathway, which controls c-Myc and cyclin E.

Tu K ，Zheng X ，Zhou Z ，Li C ，Zhang J ，Gao J ，Yao Y ，Liu Q ... -  《PLoS One》

Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

Qi R ，An H ，Yu Y ，Zhang M ，Liu S ，Xu H ，Guo Z ，Cheng T ，Cao X ... -  《CANCER RESEARCH》

RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells.

Gao J ，Chen Y ，Wu KC ，Liu J ，Zhao YQ ，Pan YL ，Du R ，Zheng GR ，Xiong YM ，Xu HL ，Fan DM ... -  《-》