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ARPP - 19表达增加与肝细胞癌相关。

Increased ARPP-19 expression is associated with hepatocellular carcinoma.

作者信息

Song Haiyan, Pan Jielu, Liu Yang, Wen Hongzhu, Wang Lei, Cui Jiefeng, Liu Yinkun, Hu Bing, Yao Zemin, Ji Guang

机构信息

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai 200032, China.

出版信息

Int J Mol Sci. 2014 Dec 24;16(1):178-92. doi: 10.3390/ijms16010178.

Abstract

The cAMP-regulated phosphoprotein 19 (ARPP-19) plays a key role in cell mitotic G2/M transition. Expression of ARPP-19 was increased in human hepatocellular carcinoma (HCC) compared to adjacent non-tumorous liver tissues in 36 paired liver samples, and the level of ARPP-19 in HCC tissues was positively correlated with the tumor size. To determine the interrelationship between ARPP-19 expression and HCC, we silenced ARPP-19 expression in the human hepatocarcinoma HepG2 and SMMC-7721 cells using lentivirus encoding ARPP-19 siRNA. HepG2 and SMMC-7721 cells with ARPP-19 knockdown displayed lowered cell growth rate, retarded colony formation and increased arrest at the G2/M phase transition. Silencing ARPP-19 in HCC cells resulted in decreased protein levels of phospho-(Ser) CDKs substrates and increased levels of inactivated cyclin division cycle 2 (Cdc2). Therefore, ARPP-19 may play a role in HCC pathogenesis through regulating cell proliferation.

摘要

环磷酸腺苷调节磷蛋白19(ARPP - 19)在细胞有丝分裂G2/M期转换中起关键作用。在36对肝脏样本中,与相邻的非肿瘤肝组织相比,人类肝细胞癌(HCC)中ARPP - 19的表达增加,且HCC组织中ARPP - 19的水平与肿瘤大小呈正相关。为了确定ARPP - 19表达与HCC之间的相互关系,我们使用编码ARPP - 19 siRNA的慢病毒在人肝癌HepG2和SMMC - 7721细胞中沉默ARPP - 19的表达。ARPP - 19敲低的HepG2和SMMC - 7721细胞显示出细胞生长速率降低、集落形成受阻以及在G2/M期转换时的阻滞增加。在HCC细胞中沉默ARPP - 19导致磷酸化(丝氨酸)周期蛋白依赖性激酶(CDKs)底物的蛋白水平降低以及失活的细胞周期蛋白分裂周期2(Cdc2)水平升高。因此,ARPP - 19可能通过调节细胞增殖在HCC发病机制中发挥作用。

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