title: Clinicopathological analysis of UHRF1 expression in medulloblastoma tissues and its regulation on tumor cell proliferation.
abstract: Studies have showed the involvement of ubiquitin-like with PHD and RING finger domains 1 (UHRF1) in tumorigenesis and progression. This study focused on the relationships between UHRF1 and medulloblastoma (MB). Immunostaining and western blotting demonstrated differential expression of UHRF1 in MB tissues and no UHRF1 expression in normal cerebellum tissues. Univariate survival analysis revealed MB patients with high UHRF1 expression had significantly shorter OS and PFS than patients with low UHRF1 (OS p = 0.009, PFS p = 0.003). Multivariate analysis illustrated that UHRF1 expression level is an independent prognostic factor influencing the OS and PFS (OS p = 0.038, PFS p = 0.014). UHRF1 expression levels were significantly different among molecular subgroups of MB (p = 0.003). Down-regulation of UHRF1 by RNAi inhibited proliferation and clonogenic ability of MB cell lines with cell cycle arrest in G1/G2-phase. Meanwhile, cells transfected with lenti-shUHRF1 showed increased p16 expression and location shift of CDK4 in MB cells. These findings indicate UHRF1 may promote cell proliferation and be a potential biomarker that can be used as a prognostic parameter and a therapeutic target for MB.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China.|Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University, Jianshe Dong Road 1, Zhengzhou, 450001, Henan, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Cai
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Jianshe Dong Road 1, Zhengzhou, 450001, Henan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Ping
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China. yu_yao@fudan.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China. maoying@fudan.edu.cn.|State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, 200032, China. maoying@fudan.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016612:Paraffin Embedding; D011379:Prognosis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D016707:Tissue Fixation; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Medulloblastoma; P16; Prognosis; Proliferation; UHRF1