title: G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells.
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.
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Tianhao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Sujun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02215, USA.
authors.forename: X
authors.initials: X
authors.lastname: Shirley Liu
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
authors.forename: Gening
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.|School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.|Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, China.
authors.forename: Fan
authors.identifier: 0000-0003-4068-3726
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006649:Histocompatibility Antigens; D009363:Neoplasm Proteins; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; D020170:Caspase 1