TY - JOUR
T1 - G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells
AU - Huang, Tianhao
AU - Zhang, Peng
AU - Li, Wang
AU - Zhao, Tian
AU - Zhang, Zhixiong
AU - Chen, Sujun
AU - Yang, Yan
AU - Feng, Yonghong
AU - Li, Fei
AU - Shirley Liu, X.
AU - Zhang, Lei
AU - Jiang, Gening
AU - Zhang, Fan
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1038/cddis.2017.65
DO - 10.1038/cddis.2017.65
M3 - Article
C2 - 28383547
AN - SCOPUS:85026746008
SN - 2041-4889
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 4
M1 - e2726
ER -