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Oct4 在 HCC 中的表达及其对 wnt/β-catenin 和 TGF-β 信号通路的调节。

Expression of Oct4 in HCC and modulation to wnt/β-catenin and TGF-β signal pathways.

机构信息

Institute of Liver Surgery, DongFeng Hospital, YunYang Medical College, Shiyan, Hubei, China.

出版信息

Mol Cell Biochem. 2010 Oct;343(1-2):155-62. doi: 10.1007/s11010-010-0509-3. Epub 2010 Jun 15.

DOI:10.1007/s11010-010-0509-3
PMID:20549546
Abstract

Hepatocellular carcinoma (HCC) is considered as a disease of dysfunction of the stem cells. Studies on stem cells have demonstrated that Oct4 plays a pivotal role in embryo regulation. In order to understand the role of Oct4 in HCC and the relationship among Oct4 and wnt/β-catenin and TGF-β signal pathways, we have detected the expression of Oct4, Nanog, Sox2, STAT3 as well as the genes in wnt/β-catenin, and TGF-β families in HCC cell lines and in tumor specimens from HCC patients. The authors found that Oct4 was expressed in all of the four HCC cell lines and the tumor specimens from HCC patients. Some other genes were also expressed in them with different level including Nanog, Sox2, STAT3 and TCF3, wnt10b, β-catenin, ELF, Smad3 and Smad4. The ability of the clone formation and migration of the HepG2 decreased after Oct4 was knockdowned. Silencing of Oct4 and TCF3 in HCC cell line HepG2 revealed that there were complicated relationships among Oct4, wnt/β-catenin family and TGF-β family genes. Knockdowning Oct4 reduced the expression of TGF-β family genes ELF, Smad3, Smad4 and wnt/β-catenin family genes, wnt10b, and β-catenin but increased TCF3. In reverse, knockdowning TCF3 led to the increased expression of Oct4 and TGF-β family genes. In conclusion, the expression of Oct4 in HCC may play an important role as in stem cell. Because Oct4 improves not only the function of wnt/β-catenin, but also the TGF-β signal pathways, the significance of its expression in HCC might be more complicated than we evinced before.

摘要

肝细胞癌(HCC)被认为是一种干细胞功能障碍疾病。干细胞研究表明,Oct4 在胚胎调控中发挥着关键作用。为了了解 Oct4 在 HCC 中的作用以及 Oct4 与 wnt/β-catenin 和 TGF-β 信号通路之间的关系,我们检测了 HCC 细胞系和 HCC 患者肿瘤标本中 Oct4、Nanog、Sox2、STAT3 以及 wnt/β-catenin 和 TGF-β 家族基因的表达。作者发现 Oct4 在所有四种 HCC 细胞系和 HCC 患者的肿瘤标本中均有表达。其他一些基因也有不同程度的表达,包括 Nanog、Sox2、STAT3 和 TCF3、wnt10b、β-catenin、ELF、Smad3 和 Smad4。Oct4 敲低后,HepG2 细胞的克隆形成和迁移能力降低。在 HCC 细胞系 HepG2 中沉默 Oct4 和 TCF3 表明,Oct4 与 wnt/β-catenin 家族和 TGF-β 家族基因之间存在复杂的关系。敲低 Oct4 降低了 TGF-β 家族基因 ELF、Smad3、Smad4 和 wnt/β-catenin 家族基因 wnt10b 和 β-catenin 的表达,但增加了 TCF3。相反,敲低 TCF3 导致 Oct4 和 TGF-β 家族基因的表达增加。总之,Oct4 在 HCC 中的表达可能像在干细胞中一样发挥重要作用。由于 Oct4 不仅改善了 wnt/β-catenin 的功能,而且还改善了 TGF-β 信号通路,因此其在 HCC 中的表达意义可能比我们之前所表现的更为复杂。

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