PBRM1 suppresses bladder cancer by cyclin B1 induced cell cycle arrest.

Abstract

Growing evidence indicates that dys-regulation of PBRM1 contributes to tumorigenesis. However, little is known about the biological function of PBRM1 in the development or progression of bladder cancer. In this study, we aimed to elucidate the pathophysiological role of PBRM1 in bladder cancer. We assessed the expression of PBRM1 in 64 bladder cancer tissue samples with matching normal tissues. We explored the biological functions of PBRM1 both in vitro and in vivo. Mutational status of PBRM1 was analyzed. Effect of PBRM1 on cell cycle was evaluated. qRT-PCR and Western blot were carried out to evaluate the expression of cyclins affected by PBRM1. Our results showed that PBRM1 expression was significantly reduced in bladder cancer cells and tissues compared to their normal counterparts. The reduced expression of PBRM1 was associated with advanced tumor stage, low differentiation grade and worse patient outcome. Further functional analysis demonstrated that PBRM1 suppressed bladder cancer cell proliferation, migration, colony formation in vitro and tumorigenicity in vivo. Genetic alteration analysis showed no amino-acid sequence altering mutations. We found that PBRM1 could block the G2/M transition by repressing cyclin B1. Our data indicated that PBRM1 functions as a tumor suppressor in bladder cancer by repressing cyclin B1 expression.

• Authors: Li Huang, Yang Peng, Guangzheng Zhong, Weibin Xie, Wen Dong, Bo Wang, Xu Chen, Peng Gu, Wang He, Shaoxu Wu, Tianxin Lin, Jian Huang
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 18 Pg. 16366-78 (Jun 30 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25978027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCNB1 protein, human
• Cyclin B1
• DNA-Binding Proteins
• Nuclear Proteins
• PBRM1 protein, human
• RNA, Messenger
• RNA, Small Interfering
• Transcription Factors

Topics

• Adult
• Aged
• Animals
• Base Sequence
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cyclin B1 (metabolism)
• DNA-Binding Proteins
• Female
• G2 Phase Cell Cycle Checkpoints (genetics)
• Genes, Tumor Suppressor
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Nuclear Proteins (biosynthesis, genetics)
• RNA Interference
• RNA, Messenger (biosynthesis)
• RNA, Small Interfering
• Transcription Factors (biosynthesis, genetics)
• Urinary Bladder Neoplasms (genetics, mortality)