Dong Lei, Zhu Jianjun, Wen Xiaoxia, Jiang Tingting, Chen Yao
Department of Anatomy, Basic Medical and Forensic Medical Institute, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2014 Apr;7(4):1203-1208. doi: 10.3892/ol.2014.1866. Epub 2014 Feb 11.
The SET oncoprotein is involved in cancer progression by modulating multiple cellular processes, including the inhibition of the tumor suppressor, protein phosphatase 2 (PP2A). Based upon these multiple activities, we hypothesized that targeted inhibition of SET is likely to have multiple discrete and measurable effects on cancer cells. In the present study, the mRNA expression levels of , and - were examined in 31 pairs of human colorectal adenocarcinoma tissues and corresponding adjacent normal colorectal tissues by quantitative real-time polymerase chain reaction (qPCR). A small interfering RNA targeting was transfected into the human colon carcinoma cell lines, LS174T and SW480. The mRNA levels of -, , and were determined by qPCR analysis and the protein levels of SET, c-Myc, PP2A and β-catenin were examined by western blot analysis. mRNA expression levels of and were found to be elevated in 22 (70.9%) samples, while PP2A expression levels were upregulated in eight (25.8%) samples. In addition, the knockdown of mRNA expression caused the upregulation of and in the two cell lines, whereas and mRNA expression was downregulated. Consistent with these results, the protein expression of β-catenin and c-Myc was found to be downregulated, whereas PP2A was upregulated at the protein level. Based on these results, we proposed that SET is essential in the carcinogenesis of human colorectal adenocarcinoma. In addition, it is suggested that SET promotes carcinogenesis through regulation of the Wnt signaling pathway.
SET癌蛋白通过调节多种细胞过程参与癌症进展，包括抑制肿瘤抑制因子蛋白磷酸酶2（PP2A）。基于这些多种活性，我们推测靶向抑制SET可能对癌细胞产生多种离散且可测量的影响。在本研究中，通过定量实时聚合酶链反应（qPCR）检测了31对人结肠腺癌组织及相应的相邻正常结肠组织中、和的mRNA表达水平。将靶向的小干扰RNA转染到人结肠癌细胞系LS174T和SW480中。通过qPCR分析测定、、和的mRNA水平，并通过蛋白质印迹分析检测SET、c-Myc、PP2A和β-连环蛋白的蛋白质水平。发现22个（70.9%）样本中的和mRNA表达水平升高，而8个（25.8%）样本中的PP2A表达水平上调。此外，敲低mRNA表达导致两种细胞系中和上调，而和mRNA表达下调。与这些结果一致，发现β-连环蛋白和c-Myc的蛋白质表达下调，而PP2A在蛋白质水平上调。基于这些结果，我们提出SET在人结肠腺癌的致癌过程中至关重要。此外，提示SET通过调节Wnt信号通路促进致癌作用。
