Shen Shasha, Gong Jiaojiao, Yang Yixuan, Qin Si, Huang Lifan, She Sha, Yang Min, Ren Hong, Hu Huaidong
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
Int J Oncol. 2017 Apr;50(4):1289-1298. doi: 10.3892/ijo.2017.3911. Epub 2017 Mar 13.
Hepatocellular carcinoma (HCC) is one of most common malignant cancers and is the second leading cause of cancer related deaths. The prognosis and survival of patients are closely related to the degree of tumor metastasis. The mechanism of HCC metastasis is still unclear. In the present study, we investigated the molecular mechanism of C-reaction protein in promoting migration and invasion of hepatocellular carcinoma cells in vitro. We estimated that CRP is overexpressed in liver cancer tissues and that it promotes invasion and metastasis of HCC in vitro. In the present study, we employed iTRAQ-based mass spectrometry to analyze the HepG2 secretory proteins of CRP siRNA-treated cells and negative control siRNA-treated cells. We identified 109 differentially expressed proteins after silencing CRP, of which 45 were upregulated and 64 were downregulated. Some of the differentially expressed proteins were confirmed by western blot analysis and real-time quantitative PCR. Furthermore, we found that knockdown of CRP substantially abrogates HIF-1α expression levels, the luciferase activity of HIF-1α and ERK and Akt phosphorylation in HepG2 cells. The present study provides a novel mechanism by which CRP promotes the proliferation, migration, invasion and metastasis of hepatocellular carcinoma cells. Inhibition of CRP suppressed migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α activity and CTSD.
肝细胞癌（HCC）是最常见的恶性肿瘤之一，也是癌症相关死亡的第二大主要原因。患者的预后和生存与肿瘤转移程度密切相关。HCC转移的机制仍不清楚。在本研究中，我们调查了C反应蛋白在体外促进肝癌细胞迁移和侵袭的分子机制。我们估计CRP在肝癌组织中过表达，并且它在体外促进HCC的侵袭和转移。在本研究中，我们采用基于iTRAQ的质谱分析法分析经CRP siRNA处理的细胞和经阴性对照siRNA处理的细胞的HepG2分泌蛋白。沉默CRP后，我们鉴定出109种差异表达蛋白，其中45种上调，64种下调。一些差异表达蛋白通过蛋白质印迹分析和实时定量PCR得到证实。此外，我们发现敲低CRP可显著消除HepG2细胞中HIF-1α的表达水平、HIF-1α的荧光素酶活性以及ERK和Akt的磷酸化。本研究提供了一种新机制，通过该机制CRP促进肝癌细胞的增殖、迁移、侵袭和转移。抑制CRP通过降低HIF-1α活性和CTSD来抑制肝癌细胞的迁移、侵袭和愈合。
