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The histone methyltransferase Wolf–Hirschhorn syndrome candidate 1‐like 1 (WHSC1L1) is involved in human carcinogenesis
Author(s) -
Kang Daechun,
Cho HyunSoo,
Toyokawa Gouji,
Kogure Masaharu,
Yamane Yuka,
Iwai Yukiko,
Hayami Shinya,
Tsunoda Tatsuhiko,
Field Helen I.,
Matsuda Koichi,
Neal David E.,
Ponder Bruce A. J.,
Maehara Yoshihiko,
Nakamura Yusuke,
Hamamoto Ryuji
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22012
Subject(s) - biology , carcinogenesis , cancer research , gene knockdown , methyltransferase , chromatin , histone , histone methyltransferase , cell cycle , lung cancer , cancer , methylation , gene , genetics , pathology , medicine
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. © 2012 Wiley Periodicals, Inc.