Latexin exhibits tumor suppressor potential in hepatocellular carcinoma
Latexin exhibits tumor suppressor potential in hepatocellular carcinoma
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Latexin 在肝细胞癌中表现出肿瘤抑制潜力
DOI：
10.3892/or.2014.2966
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发表时间：
2014-03-01
期刊：
影响因子：
4.2
通讯作者：
Kong, Lian-Bao
中科院分区：
文献类型：
--
作者：
Ni, Qing-Feng;Tian, Yuan;Kong, Lian-Bao
肝细胞癌（HCC）是最常见的原发性肝癌，latexin在几种类型的人类癌症中下调。然而，latexin在HCC中的表达仍然未知。采用半定量PCR和实时荧光定量PCR检测肝癌组织及肝癌细胞株latexin mRNA的表达，免疫组化检测latexin蛋白的表达。在体外和体内研究了latexin在肝癌衍生细胞增殖调节中的作用。流式细胞仪检测SK-hep-1和YY-8103细胞周期分布。在60例配对的HCC标本中，与癌旁组织相比，latexin mRNA在42例标本中表达下调。免疫组化分析显示，与对照组织相比，HCC中latexin表达显著降低。Latexin过表达抑制SK-hep-1和HepG 2细胞集落形成和肿瘤生长。相反，用shRNA转染的YY-8103和Focus细胞增强了集落形成和肿瘤生长。Latexin过表达可促进SK-hep-1细胞周期阻滞于G 0/G1期，而Latexin沉默可促进YY-8103细胞周期由G 0/G1期向S期转变。细胞周期蛋白依赖性激酶抑制剂（CDKIs）（p21 Cip 1、p27 Kip 1、p15 INK 4 B）、细胞周期蛋白D1和细胞周期蛋白E在Latexin过度表达的细胞和Latexin沉默的细胞中显示差异表达。这些结果表明，latexin可能是一个有效的基因治疗的目标。
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and latexin is downregulated in several types of human cancer. However, latexin expression in HCC remains unknown. mRNA expression of latexin in HCC samples and HCC-derived cell lines was detected by semi-quantitative PCR and real-time PCR, while protein expression was assessed by immunohistochemistry. The role of latexin in the regulation of the proliferation of HCC-derived cells was investigated both in vitro and in vivo. Flow cytometry was used to differentiate cell cycle distribution in SK-hep-1 and YY-8103. In a total of 60 paired HCC specimens, compared with adjacent non-cancer tissues, latexin mRNA was downregulated in 42 specimens. Immunohistochemical analysis showed a significant reduction in latexin expression in HCC compared to control tissues. Overexpression of latexin inhibited SK-hep-1 and HepG2 cellular colony formation and tumor growth. Conversely, YY-8103 and Focus cells transfected with shRNA enhanced colony formation and tumor growth. Latexin overexpression promoted cell cycle arrest in the G0/G1 phase in SK-hep-1 and silencing of latexin promoted the cell cycle transition from G0/G1 phase to S phase in YY-8103. The cyclin-dependent kinase inhibitors (CDKIs) (p21Cip1, p27Kip1, p15INK4B), cyclin D1 and cyclin E were shown to be differentially expressed in latexin-overexpressed cells and latexin-silenced cells. These results indicated that latexin may be an effective target for gene therapy.