Decreased CUL4B expression inhibits malignant proliferation of glioma in vitro and in vivo.

Abstract

OBJECTIVE: Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase complex (CRL4B) that plays a role in proteolysis and is implicated in tumorigenesis. However, little is known about CUL4B function in human brain tumors, including glioma. MATERIALS AND METHODS: Here, to investigate the involvement of CUL4B in glioma tumorigenesis, endogenous CUL4B expression was depleted in glioblastoma cell lines U87 and U251 by RNA interference (RNAi). RESULTS: Knockdown of CUL4B via shRNA-delivering lentiviruses significantly decreased cell proliferation and colony formation, causing G1 phase cell cycle arrest in both cell lines via down-regulation of cyclin D1 and up-regulation of p16. While increasing the expression of the tumor suppressor PTEN, CUL4B knockdown alleviated in vivo tumorigenesis in glioma xenograft nude mice and impeded cell migration via suppression of MMP-9. CONCLUSIONS: Therefore, knockdown of CUL4B is likely to provide a novel alternative for targeted therapy of glioma deserving further investigation.