2. Academic Validation
  3. G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells

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

  • Cell Death Dis. 2017 Apr 6;8(4):e2726. doi: 10.1038/cddis.2017.65.
Tianhao Huang 1 2 3,  Peng Zhang 4,  Wang Li 1 2 3,  Tian Zhao 1 2 3,  Zhixiong Zhang 1 2 3,  Sujun Chen 3,  Yan Yang 1 2 3,  Yonghong Feng 1,  Fei Li 5,  X Shirley Liu 6,  Lei Zhang 4,  Gening Jiang 4,  Fan Zhang 1 2 3 4
Affiliations

Affiliations

  • 1 Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
  • 2 Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
  • 3 School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
  • 4 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
  • 5 Department of Biology, New York University, New York, NY 10003, USA.
  • 6 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02215, USA.
PMID: 28383547 DOI: 10.1038/cddis.2017.65
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.

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