G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells

Tianhao Huang, Peng Zhang, Wang Li, Tian Zhao, Zhixiong Zhang, Sujun Chen, Yan Yang, Yonghong Feng, Fei Li, X. Shirley Liu, Lei Zhang, Gening Jiang, Fan Zhang

Research output: Contribution to journalArticle

Abstract

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. Although epigenetic deregulation is known to be important for tumor progression, the molecular mechanisms in NSCLC remain unclear. Here, we found that G9A (known as EHMT2), a histone methyltransferase responsible for mono-or di-methylation of histone 3 (H3) lysine 9 (K9), is significantly upregulated in NSCLC. Knocking down G9A or pharmacological inhibition of its activity suppressed tumor cell growth, colony formation, invasion and migration. Furthermore, G9A exerts these functions by repressing CASP1 expression. Knocking down CASP1 in G9A-deficient cell restored capacities of tumor cell invasion and migration. Mechanistically, G9A silences the CASP1 promoter activity by increasing H3K9me2 around its promoter. Finally, high expression of G9A or low expression of CASP1 is correlated with poor overall survival in lung adenocarcinoma. Overall, our study uncovers a novel mechanism of G9A promoting tumor cell growth and invasion by silencing CASP1, and implies that G9A may serve as a therapeutic target in treating NSCLC.

Original languageEnglish (US)
Article numbere2726
JournalCell Death and Disease
Volume8
Issue number4
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Huang, T., Zhang, P., Li, W., Zhao, T., Zhang, Z., Chen, S., Yang, Y., Feng, Y., Li, F., Shirley Liu, X., Zhang, L., Jiang, G., & Zhang, F. (2017). G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells. Cell Death and Disease, 8(4), [e2726]. https://doi.org/10.1038/cddis.2017.65