Depletion of JARID1B induces cellular senescence in human colorectal cancer

作者：Ohta Katsuya; Haraguchi Naotsugu; Kano Yoshihiro; Kagawa Yoshinori; Konno Masamitsu; Nishikawa Shimpei; Hamabe Atsushi; Hasegawa Shinichiro; Ogawa Hisataka; Fukusumi Takahito; Uemura Mamoru; Nishimura Junichi; Hata Taishi; Takemasa Ichiro; Mizushima Tsunekazu; Noguchi Yuko; Ozaki Miyuki; Kudo Toshihiro; Sakai Daisuke; Satoh Taroh; Fukami Miwa; Ishii Masaru; Yamamoto Hirofumi; Doki Yuichiro; Mori Masaki^*; Ishii Hideshi

来源：International Journal of Oncology, 2013, 42(4): 1212-1218.

DOI：10.3892/ijo.2013.1799

• jumonji
• AT rich interactive domain 1B
• H3K4 demethylase
• epigenome
• tumor suppressor genes
• cellular senescence
• colorectal cancer

The global incidence of colorectal cancer (CRC) is increasing. Although there are emerging epigenetic factors that contribute to the occurrence, development and metastasis of CRC, the biological significance of epigenetic molecular regulation in different subpopulations such as cancer stem cells remains to be elucidated. In this study, we investigated the functional roles of the H3K4 demethylase, jumonji, AT rich interactive domain 1B (JARID1B), an epigenetic factor required for the continuous cell growth of melanomas, in CRC. We found that CD44(+)/aldehyde dehydrogenase (ALDH)(+) slowly proliferating immature CRC stem cell populations expressed relatively low levels of JARID1B and the differentiation marker, CD20, as well as relatively high levels of the tumor suppressor, p16/INK4A. Of note, lentiviral-mediated continuous JARID1B depletion resulted in the loss of epithelial differentiation and suppressed CRC cell growth, which was associated with the induction of phosphorylation by the c-Jun N-terminal kinase (Jnk/Sapk) and senescence-associated beta-galactosidase activity.

• 出版日期2013-4