Fig. 9: A model for the HBP1-dependent regulation of cell cycle in NPC cells
MiR-29c inhibited HBP1 expression by targeting the HBP1 3’UTR. However, HBP1 expedited the G1 to S phase progression for promoting cell growth and proliferation by inhibiting p21 and p27 and simultaneously inducing CCND1 and CCND3 expression. On one hand, HBP1 binds to the CCND1 and CCND3 promoters and activates their transcription. HBP1 also bind to the p16INK4A, CDK4, and CDK6 promoters but does not affect their expression, it may explain, in part, HBP1 bounds to p16INK4A and CDK4 promoters that competitively inhibits the effects of p16 inhibiting CDK4, thus, the effects of CCND1-CDK4 and CCND3-CDK6 complexes may be promoted and downstream cell cycle effectors may be activated. Subsequently, it facilitates CCND1-CDK4, CCND3-CDK6 and promotes the phosphorylation of p107 and pRB, respectively. On the other hand, HBP1 binds to the p21Waft/Cip1 promoter and inhibits its transcription, thus inhibiting the effect of CDK2 due to p21Waft/Cip1 was removal. HBP1 also inhibits p27Kip1 expression and in turn the CDK2-CCNE1 complex activates the phosphorylation of pRB. Hereon, the transcription of S-phase related genes were activated including cyclin A, cyclin E, E2F-1, DP-1, etc., which accelerates the G1-to-S phase transition
