Premium
The JmjC domain‐containing histone demethylase KDM3A is a positive regulator of the G 1 /S transition in cancer cells via transcriptional regulation of the HOXA1 gene
Author(s) -
Cho HyunSoo,
Toyokawa Gouji,
Daigo Yataro,
Hayami Shinya,
Masuda Ken,
Ikawa Noriko,
Yamane Yuka,
Maejima Kazuhiro,
Tsunoda Tatsuhiko,
Field Helen I.,
Kelly John D.,
Neal David E.,
Ponder Bruce A.J.,
Maehara Yoshihiko,
Nakamura Yusuke,
Hamamoto Ryuji
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26501
Subject(s) - demethylase , biology , cancer research , histone , histone h3 , cancer cell , cancer , transcriptional regulation , bladder cancer , regulation of gene expression , cancer epigenetics , gene expression , microbiology and biotechnology , histone methyltransferase , gene , genetics
A number of histone demethylases have been identified and biochemically characterized, yet their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. In this study, we describe important roles for the histone demethylase KDM3A, also known as JMJD1A, in human carcinogensis. Expression levels of KDM3A were significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues ( p < 0.0001), when assessed by real‐time PCR. We confirmed that some other cancers including lung cancer also overexpressed KDM3A , using cDNA microarray analysis. Treatment of cancer cell lines with small interfering RNA targeting KDM3A significantly knocked down its expression and resulted in the suppression of proliferation. Importantly, we found that KDM3A activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di‐methylation by binding to its promoter region. Indeed, expression levels of KDM3A and HOXA1 in several types of cancer cell lines and bladder cancer samples were statistically correlated. We observed the down‐regulation of HOXA1 as well as CCND1 after treatment with KDM3A siRNA, indicating G 1 arrest of cancer cells. Together, our results suggest that elevated expression of KDM3A plays a critical role in the growth of cancer cells, and further studies may reveal a cancer therapeutic potential in KDM3A inhibition.