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UHRF1表达升高通过促进肝细胞癌的细胞增殖和转移导致预后不良。

Elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in hepatocellular carcinoma.

作者信息

Liu Xincheng, Ou Huohui, Xiang Leyang, Li Xianghong, Huang Yu, Yang Dinghua

机构信息

Department of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, China.

The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.

出版信息

Oncotarget. 2017 Feb 7;8(6):10510-10522. doi: 10.18632/oncotarget.14446.

Abstract

Ubiquitin-like with plant homeodomain and ring finger domains, 1 (UHRF1) is overexpressed in a variety of tumor tissues and is negatively correlated with prognosis of patients with cancers, yet so far, a comprehensive study of UHRF1 in hepatocellular carcinoma (HCC) has not been conducted. The present study was designed to explore the expression of UHRF1, associated clinical implications, and its possible functions in HCC. Reverse transcription-polymerase chain reaction and immunohistochemical staining were used to detect UHRF1 expression in HCC specimens including cancerous and noncancerous tissues. Associations of UHRF1 expression with demographic and clinicopathologic features in HCC were analyzed, and the effects of RNA interference of UHRF1 on cell proliferation, cell cycle, apoptosis, and migration were investigated in vitro and in vivo. UHRF1 mRNA and protein expression were both upregulated and negatively correlated with prognosis in HCC patients. Furthermore, inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression were observed in vitro and in vivo after UHRF1 knockdown, moreover, G2/M arrest was detected in HCC cells. In conclusion, elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in HCC.

摘要

含植物同源结构域和泛素样结构域及环状结构域蛋白1(UHRF1)在多种肿瘤组织中过表达,且与癌症患者的预后呈负相关,但迄今为止,尚未对肝细胞癌(HCC)中的UHRF1进行全面研究。本研究旨在探讨UHRF1在HCC中的表达、相关临床意义及其可能的功能。采用逆转录聚合酶链反应和免疫组织化学染色检测包括癌组织和癌旁组织在内的HCC标本中UHRF1的表达。分析UHRF1表达与HCC患者人口统计学和临床病理特征的相关性,并在体外和体内研究UHRF1的RNA干扰对细胞增殖、细胞周期、凋亡和迁移的影响。UHRF1 mRNA和蛋白表达均上调,且与HCC患者的预后呈负相关。此外,UHRF1基因敲低后,在体外和体内均观察到细胞增殖、迁移、侵袭及上皮-间质转化进程受到抑制,而且在HCC细胞中检测到G2/M期阻滞。总之,UHRF1表达升高通过促进HCC细胞增殖和转移导致预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf19/5354676/2843b87e31ce/oncotarget-08-10510-g001.jpg

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