title: Upregulated UHRF1 promotes bladder cancer cell invasion by epigenetic silencing of KiSS1.
abstract: Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression. KiSS1 functions as a metastasis suppressor in various cancers, and epigenetic silencing of KiSS1 increases the metastatic potential of cancer cells. We therefore investigated whether UHRF1 promotes bladder cancer cell invasion by inhibiting KiSS1. The expression levels of UHRF1 and KiSS1 were examined by quantitative real-time PCR assay in vitro and in vivo. The role of UHRF1 in regulating bladder cancer metastasis was evaluated in bladder cancer cell. We found that UHRF1 levels are upregulated in most clinical specimens of bladder cancer when compared with paired normal tissues, and UHRF1 expression levels are significantly increased in primary tumors that subsequently metastasized compared with non-metastatic tumors. Forced expression of UHRF1 promotes bladder cancer cell invasion, whereas UHRF1 knockdown decreases cell invasion. Overexpression of UHRF1 increases the methylation of CpG nucleotides and reduces the expression of KiSS1. UHRF1 and KiSS1 expression level is negatively correlated in vivo and in vitro. Knockdown of KiSS1 promotes bladder cancer cell invasion. Importantly, forced expression of KiSS1 partly abrogates UHRF1-induced cell invasion. These data demonstrated that upregulated UHRF1 increases bladder cancer cell invasion by epigenetic silencing of KiSS1.
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Urology, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Urology, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Urology, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Urology, Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D059648:Kisspeptins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D044767:Ubiquitin-Protein Ligases; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C106628:KISS1 protein, human; D059648:Kisspeptins; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases