title: Knockdown of RNF2 induces cell cycle arrest and apoptosis in prostate cancer cells through the upregulation of TXNIP.
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.
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.
authors.forename: Dian
authors.initials: D
authors.lastname: Jiao
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Jieheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Guoxu
authors.initials: G
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Zhangyan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Xi
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Fa
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human
keywords: RNF2; TXNIP; apoptosis; cell cycle; prostate cancer