Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma.
Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma.
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DOI：
10.1038/s41419-017-0114-4
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发表时间：
2018-02-02
影响因子：
9
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Huang Y;Wang H;Lian Y;Wu X;Zhou L;Wang J;Deng M;Huang Y
肝细胞癌（HCC）是世界范围内第三大癌症相关死亡原因，其分子发病机制和发展在很大程度上是未知的。在本研究中，基于Oncomine数据库的荟萃分析，我们发现KIF 4A表达在HCC中上调（678个样本，P = 2.03E-8）。我们进一步证实了KIF 4A mRNA和蛋白表达在人HCC肿瘤组织以及癌细胞系中过表达。在HCC患者中，KIF 4A高表达与总生存率（P < 0.0001）和无病生存率（P < 0.0337）相关。我们构建了体外KIF 4A过表达和缺失HCC细胞模型。KIF 4A过表达显著增强细胞增殖和克隆形成能力，而KIF 4A缺失导致染色体分离异常的细胞急剧增加，随后导致HCC细胞凋亡增加。此外，我们证明KIF 4A缺失与Akt激酶活性的抑制和内源性凋亡信号通路的诱导有关。综上所述，KIF 4A可以作为人类HCC的预后生物标志物和潜在的治疗靶点。
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death worldwide, and the molecular pathogenesis and development of HCC are largely unknown. In the present study, we found that KIF4A expression was upregulated in HCC (678 samples, P = 2.03E-8) based on a meta-analysis of Oncomine database. We further confirmed that both KIF4A mRNA and protein expressions were overexpressed in human HCC tumour tissues as well as cancer cell lines. Higher KIF4A expression was correlated with poorer overall survival (P < 0.0001) and disease-free survival (P < 0.0337) in HCC patients. We constructed in vitro KIF4A overexpression and depletion HCC cell models. KIF4A overexpression significantly enhanced cellular proliferation and clonogenic abilities, whereas KIF4A depletion caused a dramatic increase of cells with abnormal chromosome segregation and subsequently resulted in augmentation of apoptosis in HCC cells. In addition, we demonstrated that KIF4A depletion was related to inhibition of Akt kinase activity and induction of intrinsic apoptosis signaling pathway. Taken together, KIF4A may act as a prognostic biomarker and potential therapeutic target in human HCC.
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HBV核心启动子突变和AKT上调S期激酶相关蛋白2促进术后肝细胞癌进展
影响因子：
4.6
作者：
Chen L;Gu L;Gu Y;Wang H;Deng M;Stamataki Z;Oo YH;Huang Y
通讯作者：
Huang Y
DOI：
10.1083/jcb.200401142
发表时间：
2004-08-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mazumdar M;Sundareshan S;Misteli T
通讯作者：
Misteli T
影响因子：
4.8
作者：
Rhodes, DR;Yu, JJ;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
影响因子：
11.2
作者：
Roessler S;Jia HL;Budhu A;Forgues M;Ye QH;Lee JS;Thorgeirsson SS;Sun Z;Tang ZY;Qin LX;Wang XW
通讯作者：
Wang XW
影响因子：
29.4
作者：
Calvisi, Diego F.;Ladu, Sara;Pascale, Rosa M.
通讯作者：
Pascale, Rosa M.