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Genome-wide transcriptional analysis of apoptosis-related genes and pathways regulated by H2AX in lung cancer A549 cells

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Abstract

Histone H2AX is a novel tumor suppressor protein and plays an important role in apoptosis of cancer cells. However, the role of H2AX in lung cancer cells is unclear. The detailed mechanism and epigenetic regulation by H2AX remain elusive in cancer cells. We showed that H2AX was involved in apoptosis of lung cancer A549 cells as in other tumor cells. Knockdown of H2AX strongly suppressed apoptosis of A549 cells. We clarified the molecular mechanisms of apoptosis regulated by H2AX based on genome-wide transcriptional analysis. Microarray data analysis demonstrated that H2AX knockdown in A549 cells affected expression of 3,461 genes, including upregulation of 1,435 and downregulation of 2,026. These differentially expressed genes were subjected to bioinformatic analysis for exploring biological processes regulated by H2AX in lung cancer cells. Gene ontology analysis showed that H2AX affected expression of many genes, through which, many important functions including response to stimuli, gene expression, and apoptosis were involved in apoptotic regulation of lung cancer cells. Pathway analysis identified the mitogen-activated protein kinase signaling pathway and apoptosis as the most important pathways targeted by H2AX. Signal transduction pathway networks analysis and chromatin immunoprecipitation assay showed that two core genes, NFKB1 and JUN, were involved in apoptosis regulated by H2AX in lung cancer cells. Taken together, these data provide compelling clues for further exploration of H2AX function in cancer cells.

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Acknowledgments

The authors wish to thank Dr. Hongbo Hu for providing lung cancer A549 cells. This work was supported by the National Natural Science Foundation of China (No. 81070424; No. 81272303).

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Authors and Affiliations

  1. Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing, 100142, China

    Chengrong Lu, Min Xiong, Yuan Luo, Yanjun Zhang, Yaqiong Dong, Tianhui Niu, Zhe Wang & Lianning Duan

  2. Genminiex Informatics Ltd. Co, Shanghai, 200120, China

    Jing Li

  3. Graduate School, Hebei North University, Zhangjiakou, 075000, China

    Yaqiong Dong

  4. Department of Chest Surgery, Air Force General Hospital, PLA, Beijing, 100142, China

    Yanjun Zhu

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  1. Chengrong Lu
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  2. Min Xiong
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  3. Yuan Luo
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  4. Jing Li
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  5. Yanjun Zhang
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  6. Yaqiong Dong
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  9. Zhe Wang
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  10. Lianning Duan
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Correspondence to Chengrong Lu or Lianning Duan.

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Lu, C., Xiong, M., Luo, Y. et al. Genome-wide transcriptional analysis of apoptosis-related genes and pathways regulated by H2AX in lung cancer A549 cells. Apoptosis 18, 1039–1047 (2013). https://doi.org/10.1007/s10495-013-0875-x

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  • DOI: https://doi.org/10.1007/s10495-013-0875-x

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