Identification Of The Expression Of Transcription Factors In Cancer Stem-like Cells In Non-small Cell Lung Cancer

Background:Lung cancer is the leading cause of cancer-related mortality worldwide, and the rate is getting worse in recent years. Cancer stem cells (CSCs), a distinct population of tumor cells, are responsible for the tumor initiation, progression, metastasis, recurrence, and even resistance of treatment. Transcription factors play a key role in regulation of gene expression, not only in the differentiation of stem cells, but also essential in the reprogramming process of somatic cells to iPS cells. The research and experimentation, such as the relation between iPS factors and many kinds of cancers, the success of introducing differentiated tumor cells into stem-like cells by usage of transcription factors, Months of research and experimentation identified specific transcription factors seem to be the peculiar gene regulation process factors of CSCs, also provide a new potential therapeutic target for cancer.Objective:In this study, we identify the expression of transcription factors in cancer stem-like cells in non-small cell lung cancer. Then we explore the role of the transcription factors in CSCs and clinical significant.Methods:We collected the gathered CSCs of both NSCLC cell lines and primary lung cancer cell lines by serum-free ultra-low attachment culture, and searched for some transcription factors which showing differential expression by mRNA microarray. Then we tested cDNA and protein of those transcription factors by qRT-PCR and Western Blotting, and assessed BRF2, EGR1, ID2, PBX1, PRDM1, HES1, HEY1, RUNX2 expression in Chinese lung cancer patients through immunohistochemistry. We detected sphere forming ability using ID2 overexpression cells in vitro compared with control.Results:1. Using mRNA microarray, we found a great number of transcription factors were expressing differentially in NSCLC stem cells, such as BRF2, EGR1, ID2, PBX1, PRDM1, HES1, HEY1, RUNX2; 2. The mRNA and protein expression level of BRF2, EGR1, ID2, PBX1, PRDM1, HES1, HEY1, RUNX2 in the gathered CSCs were higher compared with control group; 3. Those transcription factors also expressed in Chinese non-small cell lung cancer patients; 4. Overexpression of ID2 led to significant increase in the number of oncospheres formed.Conclusions:Our findings demonstrate the important roles of BRF2, EGR1, ID2, PBX1, PRDM1, HES1, HEY1, RUNX2 in CSCs, and ID2 may promote the generation of CSCs in NSCLC.