Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1002/gcc.22012

Type

Journal article

Journal

Genes Chromosomes Cancer

Publication Date

02/2013

Volume

52

Pages

126 - 139

Keywords

Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cyclin G1, Female, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HEK293 Cells, HeLa Cells, Hep G2 Cells, Histone-Lysine N-Methyltransferase, Humans, Immunohistochemistry, Liver Neoplasms, Lung Neoplasms, Male, NIMA-Related Kinases, Neoplasms, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Protein-Serine-Threonine Kinases, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Urinary Bladder Neoplasms