title: The histone methyltransferase Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) is involved in human carcinogenesis.
abstract: Histone lysine methylation plays a fundamental role in chromatin organization. Although a set of histone methyltransferases have been identified and biochemically characterized, the pathological roles of their dysfunction in human cancers are still not well understood. In this study, we demonstrate important roles of WHSC1L1 in human carcinogenesis. Expression levels of WHSC1L1 transcript were significantly elevated in various human cancers including bladder carcinoma. Immunohistochemical analysis of bladder, lung, and liver cancers confirmed overexpression of WHSC1L1. WHSC1L1-specific small interfering RNAs significantly knocked down its expression and resulted in suppression of proliferation of bladder and lung cancer cell lines. WHSC1L1 knockdown induced cell cycle arrest at the G(2)/M phase followed by multinucleation of cancer cells. Expression profile analysis using Affymetrix GeneChip(®) showed that WHSC1L1 affected the expression of a number of genes including CCNG1 and NEK7, which are known to play crucial roles in the cell cycle progression at mitosis. As WHSC1L1 expression is significantly low in various normal tissues including vital organs, WHSC1L1 could be a good candidate molecule for development of novel treatment for various types of cancer.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Daechun
authors.initials: D
authors.lastname: Kang
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kogure
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamane
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Iwai
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayami
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Helen I
authors.initials: HI
authors.lastname: Field
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056766:Cyclin G1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D000072379:NIMA-Related Kinases; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C534702:CCNG1 protein, human; D056766:Cyclin G1; D009687:Nuclear Proteins; D011495:Histone-Lysine N-Methyltransferase; C432968:NSD3 protein, human; C512685:NEK7 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases