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Ubiquitin specific peptidase 33 promotes cell proliferation and reduces apoptosis through regulation of the SP1/PI3K/AKT pathway in retinoblastoma

ABSTRACT Ubiquitin-specific protease 33 (USP33), a deubiquitinating enzyme (DUB), has been identified to serve as a tumor suppressor or an oncogene in different cancers. However, its role in retinoblastoma (RB) remains unknown. Here, we aimed to uncover USP33 expression profile and function in RB, and disclose the underlying mechanism. USP33 levels in RB tissues and cells were determined using RT-qPCR and western blotting assays. USP33 effects on cell growth, cycle, apoptosis and tumorigenesis were studied using MTT, Edu, cycle and western blotting and in vivo assays. The results showed that USP33 expression levels were elevated in RB tissues and cells as compared with normal retinal tissues and cells. Downregulation of USP33 in RB Y79 and WERI-RB1 cells leaded to significant increases in cell apoptosis, G1 phase arrest and tumorigenesis, and reductions in cell growth and G2 and S phase arrest, as well as inhibited the activation of the PI3K/AKT signaling. SP1 overexpression abolished the roles of USP33 downregulation in modulating the activation of PI3K/AKT signaling, cell growth, apoptosis, and cell cycle. This study uncovered that USP33 promoted the progression of RB through regulation of the SP1/PI3K/AKT pathway.