Suppression of CK-19 expression by shRNA can inhibit the malignancy of hepatocellular carcinoma cells
Suppression of CK-19 expression by shRNA can inhibit the malignancy of hepatocellular carcinoma cells
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shRNA抑制CK-19表达可抑制肝癌细胞恶性
DOI：
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Wenming Cong
中科院分区：
文献类型：
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作者：
Wenming Cong
摘要：目的：细胞角蛋白-19（CK-19）在一种新的肝细胞癌（HCC）亚型中高度表达，该亚型同时具有肝细胞和胆管细胞分化，我们首次将其定义为双表型HCC（DPHCC）。与经典型HCC相比，DPHCC患者的临床预后更差。然而，CK-19在DPHCC发展中的作用仍不清楚。本研究的主要目的是探讨CK-19对DPHCC恶性表型的可能影响及其作为潜在治疗靶点的可能价值。方法：前瞻性检测404例临床肝癌组织中CK-19的表达，并评价其临床意义。我们还评估了CK-19的生物学功能，在体外和体内使用敲低肝癌细胞。结果：CK-19表达与肿瘤的TNM分期（p = 0.011）和血管浸润（p = 0.035）显著相关。CK-19表达阳性的患者总体生存期和无病生存期较差，而CK-19表达阴性的患者生存期更长。CK-19的敲低可降低MHCC-97 H细胞增殖（p = 0.006）和在软琼脂中形成的集落数（p = 0.0043）。在CK-19敲低细胞中，侵入基质胶包被的膜的MHCC-97 H细胞的数量减少（p = 0.038）。体内实验结果显示，CK-19基因敲减组肿瘤重量（0.257±0.081 g）明显低于阴性对照组（0.443±0.114 g）（P < 0.01）。我们的研究结果证明了CK-19表达在HCC细胞系中的生物学功能，因为抑制CK-19在体外和体内都抑制肿瘤细胞的生长。结论：因此，CK-19不仅可以作为评价DPHCC恶性程度的候选生物学指标，而且可以作为DPHCC治疗的潜在靶点。
Abstract: Objective: Cytokeratin-19 (CK-19) is highly expressed in a novel subtype of hepatocellular carcinomas (HCC) displaying both hepatocellular and cholangiocellular differentiation which we firstly defined as dual-phenotype HCC (DPHCC). Compared with patients with classical HCC, the patients with DPHCC showed worse clinical prognosis. However, the role of CK-19 in development of DPHCC remains unknown. The main purpose of the present study was to investigate the possible effect of CK-19 on the malignant phenotype of DPHCC and its possible value as a potential therapeutic target. Methods: In this study, we prospectively examined the CK-19 expression in 404 clinical HCC tissues and evaluated its clinical significance. We also evaluated the biological function of CK-19 both in vitro and in vivo using knockdown HCC cells. Results: Our results showed that CK-19 expression was significantly associated with TNM stage (p = 0.011) and vascular invasion (p = 0.035). Patients with positive CK-19 expression had poorer overall-survival and disease-free survival, whereas those with negative CK-19 expression survived longer. Knockdown of CK-19 can reduce the MHCC-97H cell proliferation (p = 0.006) and the number of colonies formed in soft agar (p = 0.0043). The number of MHCC-97H cells invading the matrigel coated membrane was decreased in CK-19 knockdown cells (p = 0.038). In addition, the in vivo experiments in mice showed the tumor weight was significantly reduced in CK-19 knockdown group (0.257±0.081 g) compared with negative control (0.443±0.114 g) (P < 0.01). Our findings demonstrated the biological function in HCC cell lines of CK-19 expression, since suppression of CK-19 inhibits the growth of tumor cells both in vitro and vivo. Conclusion: Taken together, our results implied that CK-19 not only could be a candidate pathobiological biomarker for evaluating the malignant extent of DPHCC, also could consider being a potential candidate therapy target in DPHCC.
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影响因子：
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作者：
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DOI：
10.1083/jcb.200603161
发表时间：
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