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Depletion of JARID1B induces cellular senescence in human colorectal cancer.

Authors: Ohta, K  Haraguchi, N  Kano, Y  Kagawa, Y  Konno, M  Nishikawa, S  Hamabe, A  Hasegawa, S  Ogawa, H  Fukusumi, T  Uemura, M  Nishimura, J  Hata, T  Takemasa, I  Mizushima, T  Noguchi, Y  Ozaki, M  Kudo, T  Sakai, D  Satoh, T  Fukami, M  Ishii, M  Yamamoto, H  Doki, Y  Mori, M  Ishii, H 
Citation: Ohta K, etal., Int J Oncol. 2013 Apr;42(4):1212-8. doi: 10.3892/ijo.2013.1799. Epub 2013 Jan 25.
Pubmed: (View Article at PubMed) PMID:23354547
DOI: Full-text: DOI:10.3892/ijo.2013.1799

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, lentiviralmediated 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 cJun Nterminal kinase (Jnk/Sapk) and senescenceassociated betagalactosidase activity. Moreover, green fluorescentlabeled cell tracking indicated that JARID1Bpositive CRC cells had greater tumorigenicity than JARID1Bnegative CRC cells after their subcutaneous inoculation into immunodeficient mice, although JARID1Bnegative CRC cells resumed normal growth after a month, suggesting that continuous JARID1B inhibition is necessary for tumor eradication. Thus, JARID1B plays a role in CRC maintenance. JARID1B may be a novel molecular target for therapyresistant cancer cells by the induction of cellular senescence.

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CRRD Object Information
CRRD ID: 9587777
Created: 2014-10-17
Species: All species
Last Modified: 2014-10-17
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.