title: Down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation.
abstract: G9a, a histone methyltransferase, is aberrantly expressed in some human tumor types. By comparing 182 paired colorectal cancer and peritumoral tissues, we found that G9a was highly expressed in colorectal cancer (CRC). Overexpression of G9a promoted CRC cells proliferation and colony formation, whereas knockdown of G9a inhibited CRC cells proliferation. Depletion of G9a increased the rate of chromosome aberration, induced DNA double strand breaks and CRC cells senescence. G9a inhibition synergistically increased γH2AX expression induced by topoisomerase I inhibitors and ultimately led to CRC cell death. The findings that down-regulation of G9a triggers DNA damage response and inhibits colorectal cancer cells proliferation may define G9a as potential oncotarget in CRC.
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Pengxing
authors.initials: P
authors.lastname: He
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C468783:H2AX protein, human; D006649:Histocompatibility Antigens; D006657:Histones; D059004:Topoisomerase I Inhibitors; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase