Notch2 is a crucial regulator of self-renewal and tumorigenicity in human hepatocellular carcinoma cells.
Notch2 is a crucial regulator of self-renewal and tumorigenicity in human hepatocellular carcinoma cells.
复制标题
DOI：
10.3892/or.2016.4831
复制
发表时间：
2016-07
期刊：
影响因子：
4.2
通讯作者：
Wenrui Wu;Rui Zhang;Xiang-De Shi;C. Yi;Lei-bo Xu;Chao Liu
中科院分区：
文献类型：
--
作者：
Wenrui Wu;Rui Zhang;Xiang-De Shi;C. Yi;Lei-bo Xu;Chao Liu
Notch通路在干细胞生物学和癌症中起着重要作用。据报道Notch 2在人肝细胞癌（HCC）组织中上调。然而，Notch 2在人HCC细胞中的生物学功能尚未被记录。本研究的目的是探讨其对人肝癌细胞进展的可能作用。Western blotting检测Notch 2在4株人肝癌细胞系中的表达。接下来，在人HCC细胞中通过小干扰RNA（siRNA）敲低Notch 2。通过细胞增殖试验、集落形成试验、化疗耐药试验和异种移植物形成试验研究Notch 2在人肝癌细胞中的作用。在本研究中，蛋白质印迹显示Notch 2的表达在人肝癌细胞系中上调。Notch 2基因缺失不仅显著抑制肝癌细胞的增殖、细胞周期进程和集落形成能力，而且使其对5-氟尿嘧啶（5-FU）的敏感性增加。此外，在CD 90阳性的HCC细胞中发现Notch 2上调，CD 90是肝干细胞的标志物。最重要的是，在HCC细胞中敲低Notch 2会损害体内肿瘤形成。总之，我们的研究结果表明，Notch 2可能赋予肝癌干细胞特性; Notch 2的下调抑制肝癌细胞的增殖和肿瘤形成，并增加其对5-FU的敏感性，这表明Notch 2作为肝癌的潜在治疗靶点。
The Notch pathway plays an important role in both stem cell biology and cancer. Notch2 was reported to be upregulated in human hepatocellular carcinoma (HCC) tissues. However, the biological function of Notch2 in human HCC cells has not yet been documented. The aim of this study was to investigate its possible function on the progression of human HCC cells. The expression of Notch2 was detected in four human HCC cell lines by western blotting. Next, Notch2 was knocked down by small interference RNA (siRNA) in human HCC cells. The role of Notch2 in human HCC cells was investigated by cell proliferation assay, colony formation assay, chemoresistance and xenograft formation assay. In the present study, western blotting revealed that the expression of Notch2 was upregulated in human HCC cell lines. Genetic depletion of Notch2 in HCC cells not only resulted in significantly inhibited proliferation, cell cycle progression and colony formation ability but also increased its sensitivity to 5-fluorouracil (5-FU) compared with controls. In addition, upregulation of Notch2 was discovered in CD90 positive HCC cells, CD90 is a marker of hepatic stem cells. Most importantly, knockdown of Notch2 in HCC cells impaired the tumor formation in vivo. Taken together, our findings indicate that Notch2 may confer stemness properties in HCC; downregulation of Notch2 inhibited the proliferation and tumor formation of HCC cells and increase their sensitivity to 5-FU, suggesting Notch2 as a potential therapeutic target for HCC.