Molecular chaperone HSP90 regulation of the alternative splicing of numb as a clue for HCC progression.

e15114 Background: The human NUMB gene transcript is alternatively spliced; two splice variants, PRRL and PRRS, were reported to promote the growth or differentiation, respectively, of neural cells. PRRL was recently reported to also promote the growth of breast cancer cells. However, the involvement of Numb in hepatocellular carcinoma (HCC) remains unknown. Methods: We performed immunohistochemical, western blotting and quantitative RT-PCR to examine the expression of different Numb PRR isoforms in HCC tissues and cell lines. Overexpression, siRNA-mediated knockdown and specific inhibitors were used to investigate the effects and the underlying mechanism of the two Numb isoforms on cell proliferation, invasion and migration. Results: PRRL is strongly expressed in HCC tumor tissues, while PRRS is mainly expressed in adjacent normal tissues. Elevated expression of Numb PRRL in HCC is associated with earlier recurrence and shorter overall survival of HCC patients after radical surgery. Experimentally, Numb ...