丙型肝炎病毒核心蛋白诱导胆管癌细胞上皮-间充质转化。

Epithelial-mesenchymal transition induced by hepatitis C virus core protein in cholangiocarcinoma.

机构信息

Southwest Hospital, Third Military Medical University, ChongQing, China.

出版信息

Ann Surg Oncol. 2010 Jul;17(7):1937-44. doi: 10.1245/s10434-010-0925-3. Epub 2010 Feb 17.

DOI:10.1245/s10434-010-0925-3

PMID:20162464

Abstract

BACKGROUND

Cholangiocarcinoma (CC) is associated with chronic hepatitis C virus (HCV) infection. We investigated the effect of hepatitis C virus core protein (HCVc) on epithelial-mesenchymal transition (EMT) in CC and tried to identify its target trigger.

METHODS

First, we examined expression of HCVc and epithelial and mesenchymal markers in CC tissues. Then we transient-transfected HCVc gene into a CC cell line and examined expression of lysyl oxidase-like 2 (LOXL2) and epithelial and mesenchymal markers by quantitative real-time polymerase chain reaction (PCR) and Western blotting. Finally, LOXL2 gene silencing was shown in QBC939/HCVc cells by RNA interference (RNAi), and we further examined expression of epithelial and mesenchymal markers by quantitative real-time PCR and Western blotting.

RESULTS

Through immunohistochemical staining, the present study showed that HCVc is significantly associated with CC invasion and metastasis. In vitro study showed that HCVc expression induces EMT in CC cell line QBC939, and a mechanism through LOXL2 pathway is suggested. Expression of HCVc was significantly correlated with greater migratory and invasive potential of CC cells.

CONCLUSIONS

These observations indicate that HCVc plays a critical role in promoting invasion and metastasis of CC cells.

摘要

背景

胆管癌（CC）与慢性丙型肝炎病毒（HCV）感染有关。我们研究了丙型肝炎病毒核心蛋白（HCVc）对 CC 上皮间质转化（EMT）的影响，并试图确定其靶触发因素。

方法

首先，我们检测了 CC 组织中 HCVc 和上皮及间质标志物的表达。然后，我们将 HCVc 基因瞬时转染到 CC 细胞系中，并通过实时定量聚合酶链反应（PCR）和 Western blot 检测赖氨酸氧化酶样 2（LOXL2）和上皮及间质标志物的表达。最后，通过 RNA 干扰（RNAi）沉默 QBC939/HCVc 细胞中的 LOXL2 基因，并通过实时定量 PCR 和 Western blot 进一步检测上皮和间质标志物的表达。