RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells

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• 作者：Jinghua Han^a ; ¹ ; ² ; ^{hjhtjmu@163.com} ; Fei Zhang^a ; ¹ ; ² ; Man Yu^b ; Peiqi Zhao^a ; ^c ; Wei Ji^a ; Haichang Zhang^a ; Bing Wu^a ; Yuqing Wang^a ; Ruifang Niu^a ; ^{niurf1982@yahoo.com.cn}
• 关键词：Breast cancer ; NANOG ; Proliferation ; Cell cycle ; Chromatin immunoprecipitation
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：1 August, 2012
• 卷：321
• 期：1
• 页码：80-88
• 文件大小：1211 K

摘要

Since the processes of normal embryogenesis and neoplasia share many of similar pathways, tumor development has been interpreted as an abnormal form of organogenesis. NANOG is a homeodomain-containing transcription factor that functions to maintain self-renewal and proliferation of embryonic stem cells (ESCs). Aberrant expression of NANOG has been observed in many types of human malignancies. However, its potential implication in tumorigenesis has not been fully clarified. In this study, we have employed small interference RNA (RNAi) technology to silence endogenous NANOG expression in breast cancer cells and successfully selected three independent clones with stably inhibited NANOG expression of MCF-7 cells. Functional analysis revealed that down-regulation of NANOG reduced cell proliferation, colony formation and migration ability of MCF-7 cells. Consistently, proliferation of breast cancer MDA-MB-231 cells was also significantly inhibited after the knockdown of NANOG expression. Interestingly, we found that the expression levels of cyclinD1 and c-myc were markedly down-regulated and the cell cycle were blocked at the G0/G1 phases after the knockdown of NANOG, while the expression of cyclinE and signal transducers and activators of transcription3 (STAT3) remained unaffected. In addition, the expression of NANOG and cyclinD1 can be rescued after the transfection of pcDNA3.1 (-)-NANOG expression vector into the three clones. Finally, our chromatin immunoprecipitation (ChIP) experiment showed that NANOG protein can bind to the promoter region of cyclinD1 and regulate cells cycle. Taken together, our findings may not only establish a molecular basis for the role of NANOG in modulating cell cycle progression of breast cancer cells but also suggest a potential target for the treatment of at least some subtypes of breast cancer.