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应用全基因组cDNA表达芯片杂交技术,筛查了OCT4多潜能转录因子阳性(OCT4+)的肺腺癌干细胞及其OCT4表达沉默(OCT4-KD)细胞中的差异表达基因。发现与OCT4+细胞比较,OCT4-KD细胞有2 138个基因显示差异表达,其中1 554个基因表达上调,584个基因表达下调。这些差异表达基因涉及细胞周期、细胞增殖、细胞凋亡以及细胞迁移等功能,参与肿瘤通路、EGFR信号通路和低氧/p53信号通路等多个信号转导通路。选择差异表达最显著的基因进行分析,显示其中20个基因特异性表达在OCT4+细胞,而47个基因仅在OCT4-KD细胞中表达,该组基因可以作为肺腺癌中OCT4+细胞可资鉴别的特征性基因。此外,研究还发现在肺腺癌干细胞中,OCT4表达受HIF1α调控,应用RNA干扰技术选择性灭活HIF1α基因引起OCT4表达转阴和细胞表型分化,而采用棘霉素干预HIF1α的转录活性也明显下调了OCT4表达。实验结果揭示,肺腺癌干细胞中存在HIF1-OCT4调控轴,此发现为发展OCT4靶向治疗新技术提供了研究思路。
The whole genome cDNA microarray was used to screen differentially expressed genes in OCT4 + OCT4-deficient lung adenocarcinoma stem cells and their OCT4-silenced cells (OCT4-KD). In comparison with OCT4 + cells, 2 138 genes were found to be differentially expressed in OCT4-KD cells, of which 1 554 genes were up-regulated and 584 genes were down-regulated. These differentially expressed genes involved in cell cycle, cell proliferation, apoptosis and cell migration, participate in many signal transduction pathways such as tumor pathway, EGFR signaling pathway and hypoxia / p53 signaling pathway. Twenty genes were specifically expressed in OCT4 + cells and 47 genes were only expressed in OCT4-KD cells, which can be used as a marker for OCT4 + cells in lung adenocarcinoma Characteristic gene. In addition, the study also found that in lung adenocarcinoma stem cells, OCT4 expression is regulated by HIF1α, the selective inactivation of HIF1α gene by RNAi technology leads to over-expression of OCT4 and phenotypic differentiation of cells, while the eosinophil intervention of HIF1α transcriptional activity OCT4 expression was significantly down-regulated. The experimental results revealed that HIF1-OCT4 regulatory axis exists in lung adenocarcinoma stem cells. This finding provides a research idea for the development of new technology of OCT4 targeted therapy.