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

// Ming Wei 1, * , Dian Jiao 1, * , Donghui Han 3 , Jieheng Wu 2 , Feilong Wei 2 , Guoxu Zheng 2 , Zhangyan Guo 2 , Wenjin Xi 2 , Fa Yang 3 , Pin Xie 3 , Lingling Zhang 2 , An-Gang Yang 2 , He Wang 1 , Weijun Qin 3 , Weihong Wen 2 1 Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi’an, China 2 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi’an, China 3 Department 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.