Lysine acetyltransferase GCN5 potentiates the growth of non-small cell lung cancer via promotion of E2F1, cyclin D1, and cyclin E1 expression.
The lysine acetyltransferases play crucial but complex roles in cancer development. GCN5 is a lysine acetyltransferase that generally regulates gene expression, but its role in cancer development remains largely unknown. In this study, we report that GCN5 is highly expressed in non-small cell lung cancer tissues and that its expression correlates with tumor size. We found that the expression of GCN5 promotes cell growth and the G1/S phase transition in multiple lung cancer cell lines. Further study revealed that GCN5 regulates the expression of E2F1, cyclin D1, and cyclin E1. Our reporter assays indicated that the expression of GCN5 enhances the activities of the E2F1, cyclin D1, and cyclin E1 promoters. ChIP experiments suggested that GCN5 binds directly to these promoters and increases the extent of histone acetylation within these regions. Mechanistic studies suggested that GCN5 interacts with E2F1 and is recruited by E2F1 to the E2F1, cyclin D1, and cyclin E1 promoters. The function of GCN5 in lung cancer cells is abrogated by the knockdown of E2F1. Finally, we confirmed that GCN5 regulates the expression of E2F1, cyclin D1, and cyclin E1 and potentiates lung cancer cell growth in a mouse tumor model. Taken together, our results demonstrate that GCN5 specifically potentiates lung cancer growth by directly promoting the expression of E2F1, cyclin D1, and cyclin E1 in an E2F1-dependent manner. Our study identifies a specific and novel function of GCN5 in lung cancer development and suggests that the GCN5-E2F1 interaction represents a potential target for lung cancer treatment.
['Chen|Long|L|', 'Wei|Tingyi|T|', 'Si|Xiaoxing|X|', 'Wang|Qianqian|Q|', 'Li|Yan|Y|', 'Leng|Ye|Y|', 'Deng|Anmei|A|', 'Chen|Jie|J|', 'Wang|Guiying|G|', 'Zhu|Songcheng|S|', 'Kang|Jiuhong|J|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000818:Animals D002289:Carcinoma, Non-Small-Cell Lung D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D019938:Cyclin D1 D019927:Cyclin E D050687:E2F1 Transcription Factor D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008175:Lung Neoplasms D008239:Lysine D008297:Male D051379:Mice D008819:Mice, Nude D008875:Middle Aged D009368:Neoplasm Transplantation D020411:Oligonucleotide Array Sequence Analysis D015513:Oncogene Proteins D050880:p300-CBP Transcription Factors
GCN5 Lung Cancer E2F1 Cancer Prevention Cancer biology Cell Cycle Gene Regulation Histone Acetylase Lysine Acetyltransferase (KAT)