Oncotarget

Research Papers:

Knockdown of RNF2 induces cell cycle arrest and apoptosis in prostate cancer cells through the upregulation of TXNIP

Ming Wei, Dian Jiao, Donghui Han, Jieheng Wu, Feilong Wei, Guoxu Zheng, Zhangyan Guo, Wenjin Xi, Fa Yang, Pin Xie, Lingling Zhang, An-Gang Yang, He Wang, Weijun Qin and Weihong Wen _

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Oncotarget. 2017; 8:5323-5338. https://doi.org/10.18632/oncotarget.14142

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Abstract

Ming Wei1,*, Dian Jiao1,*, Donghui Han3, Jieheng Wu2, Feilong Wei2, Guoxu Zheng2, Zhangyan Guo2, Wenjin Xi2, Fa Yang3, Pin Xie3, Lingling Zhang2, An-Gang Yang2, He Wang1, Weijun Qin3, Weihong Wen2

1Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi’an, China

2State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi’an, China

3Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi’an, China

*Co-first author

Correspondence to:

Weihong Wen, email: wenweih@fmmu.edu.cn

Weijun Qin, email: qinweij@fmmu.edu.cn

Keywords: RNF2, TXNIP, prostate cancer, cell cycle, apoptosis

Received: June 03, 2016    Accepted: November 22, 2016    Published: December 24, 2016

ABSTRACT

RNF2, also known as RING1b or RING2, is identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), which mediates the mono-ubiquitination of histone H2A. RNF2 has been proved to have oncogenic function in many kinds of cancers, but the function of RNF2 in prostate cancer (PCa) has not been evaluated. Here we show that PCa tissues showed higher RNF2 expression than the benign prostatic hyperplasia (BPH) tissues. Knockdown of RNF2 in PCa cells resulted in cell cycle arrest, increased apoptosis and inhibited cell proliferation, and the growth of RNF2 knockdown PCa xenografts were obviously inhibited in nude mice. Gene microarray analysis was performed and tumor suppressor gene TXNIP was found to be significantly increased in RNF2 knockdown cells. Simultaneously knockdown of RNF2 and TXNIP can partially rescue the arrested cell cycle, increased apoptosis and inhibited cell proliferation in RNF2 single knockdown cells. Furthermore, ChIP assay result showed that RNF2 enriched at the TXNIP promoter, and the enrichment of RNF2 and ubiquitination of H2A in TXNIP promoter was obviously inhibited in RNF2 knockdown cells. In conclusion, our results demonstrate that RNF2 functions as an oncogene in PCa and RNF2 may regulate the progression of PCa through the inhibition of TXNIP.


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