KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma.
KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma.
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KIFC1，肝细胞癌的新型潜在预后因素和治疗靶点
DOI：
10.3892/ijo.2018.4348
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发表时间：
2018-06
影响因子：
5.2
通讯作者：
Fang L
中科院分区：
文献类型：
--
作者：
Fu X;Zhu Y;Zheng B;Zou Y;Wang C;Wu P;Wang J;Chen H;Du P;Liang B;Fang L
驱动蛋白家族成员C1（KIFC 1，也称为HSET）是一种负末端导向的运动蛋白，在中心体聚集中起关键作用。本研究通过免疫组化分析研究了91例患者配对肝细胞癌（HCC）组织和癌旁非癌组织中KIFC 1的表达;同时收集了临床数据。KIFC 1在肝癌组织中的表达高于癌旁组织（54.9% vs.14.3%; P<0.01），其表达与癌栓、转移、复发及复发时间有关。Kaplan-Meier分析显示KIFC 1的表达与无瘤生存率显著相关。此外，多变量分析显示KIFC 1的过表达是HCC患者的独立预测标志物。GEPIA数据与实验结果一致。在体外，KIFC 1敲低有效地降低HCC细胞活力，并诱导细胞凋亡和细胞死亡。KIFC 1敲除还显著抑制了体外肿瘤细胞的迁移和侵袭。从机制上讲，在KIFC 1小干扰RNA处理组中，凋亡相关蛋白B细胞淋巴瘤-2（Bcl-2）下调，而Bcl-2相关X蛋白和p53水平上调。此外，当KIFC 1沉默时，磷酸化磷酸肌醇3-激酶和磷酸化AKT的表达水平显着降低。上皮-间质转化相关蛋白N-cadherin、基质金属蛋白酶-2（MMP-2）、β-catenin、Slug和锌指E-box-binding homeobox 1表达下调，而E-cadherin表达上调。KIFC 1的过表达与HCC的进展和预后密切相关，提示KIFC 1的表达水平是HCC潜在的预后生物标志物和治疗靶点。
Kinesin family member C1 (KIFC1, also known as HSET) is a minus end-directed motor protein, which is critical in centrosome clustering. The present study investigated the expression of KIFC1 in paired hepatocellular carcinoma (HCC) tissues and adjacent non-cancerous tissues from 91 patients by immunohistochemical analysis; clinical data were concomitantly collected. KIFC1 was expressed at high levels in HCC tissues, compared with that in peritumoral tissues (54.9 vs. 14.3%; P<0.01), and its expression correlated with tumor emboli, metastasis, recurrence and time of recurrence. Kaplan-Meier analysis showed that the expression of KIFC1 was significantly associated with tumor-free survival rates. In addition, multivariate analyses revealed that the overexpression of KIFC1was an independent predictive marker in patients with HCC. Consistently, data derived from GEPIA was in agreement with the results. In vitro, KIFC1 knockdown effectively decreased HCC cell viability, and induced apoptosis and cell death. KIFC1 knockdown also significantly suppressed tumor cell migration and invasion in vitro. Mechanistically, the apoptosis-related protein, B-cell lymphoma-2 (Bcl-2), was downregulated in KIFC1 small interfering RNA-treated groups, whereas thee levels of Bcl-2-associated X protein and p53 were upregulated. In addition, the expression levels of phosphorylated phosphoinositide 3-kinase and phosphorylated AKT were decreased significantly when KIFC1 was silenced. The epithelial-mesenchymal transition-related proteins, N-cadherin, matrix metalloproteinase-2 (MMP-2), β-catenin, Slug, and Zinc finger E-box-binding homeobox 1, were downregulated, whereas the expression of E-cadherin was upregulated. The overexpression of KIFC1 was correlated closely with the progression of HCC and poor prognosis, and suggested that the expression levels of KIFC1 are a potential prognostic biomarker and therapeutic target in HCC.
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影响因子：
5.2
作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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