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An epigenetic role for PRL-3 as a regulator of H3K9 methylation in colorectal cancer.

Authors: Liu, Y  Zheng, P  Liu, Y  Ji, T  Liu, X  Yao, S  Cheng, X  Li, Y  Chen, L  Xiao, Z  Zhou, J  Li, J 
Citation: Liu Y, etal., Gut. 2013 Apr;62(4):571-81. doi: 10.1136/gutjnl-2011-301059. Epub 2012 Feb 16.
Pubmed: (View Article at PubMed) PMID:22345654
DOI: Full-text: DOI:10.1136/gutjnl-2011-301059

OBJECTIVE: This study investigated the epigenetic role of PRL-3, a key metastasis gene in colorectal cancer (CRC), as a regulator of histone demethylation and the functions of Jumonji domain-containing protein 1B (JMJD1B) and JMJD2B in the progression of CRC. METHODS: PRL-3-associated proteins were analysed using functional distribution and category enrichment analysis. Western blotting and immunofluorescence were used to detect nuclear PRL-3. The relationship between PRL-3 and JMJD1B or JMJD2B and the roles of JMJD1B, JMJD2B and PRL-3 in histone demethylation were determined after these proteins were knocked down using RNA interference. Case-control studies on JMJD1B and JMJD2B in patients with CRC were performed using immunohistochemical analysis. The in vitro functional effects of JMJD2B and JMJD1B were examined further. RESULTS: JMJD1B and JMJD2B, two histone demethylases, were enriched among PRL-3-associated proteins. Nuclear PRL-3 was observed in CRC cells and clinical samples of CRC. The expression of nuclear PRL-3 was increased in patients with CRC at more advanced Dukes' stages. PRL-3 was involved in the regulation of histone methylation by affecting the activities of JMJD1B and JMJD2B. A low expression of the JMJD1B protein was positively correlated with the lymph node status (p=0.032), Dukes' classification (p=0.008) and TNM staging (p=0.022) of patients with CRC. A high expression of JMJD2B was positively correlated with the lymph node status (p=0.03), Dukes' classification (p=0.036) and tumour invasion (p=0.003) of patients with CRC. A loss-of-function analysis confirmed that JMJD2B promoted the proliferation, colony formation and migration of human CRC cells. CONCLUSION: Our data reveal a new role for PRL-3 as a key regulator of histone demethylation. JMJD1B seems to be a candidate tumour suppressor and JMJD2B seems to be a potential oncoprotein in the development and progression of CRC.

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CRRD Object Information
CRRD ID: 9586735
Created: 2014-10-03
Species: All species
Last Modified: 2014-10-03
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.