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The Research And Exploration Of JMJD2A Biological Function

Posted on:2015-03-14Degree:MasterType:Thesis
Country:ChinaCandidate:Y GaoFull Text:PDF
GTID:2250330428961904Subject:Cell biology
Abstract/Summary:PDF Full Text Request
JMJD2A, also called KDM4A or JHDM3A, is a kind of histone demethylase. It can demethylases di-/tri-methylated H3K9or H3K36to different methylated levels. It’s reported that JMJD2A is an oncogene in breast cancer cell, colon carcinoma cell, squamous-cell carcinoma cell. What’s more, JMJD2A can mediate the regulation of genes in transcriptional level by forming complexes with transcription factors. JMJD2A protein level is cell cycle-dependent and regulated by ubiquitin-protesome pathway.Our study provides new sights into the biological functions of JMJD2A:We discovered JMJD2A might be a oncogene suppresser, which might has something with p27. First of all, We found JMJD2A protein level and mRNA level both decreased in about60%HCC samples. It suggested JMJD2A might be an oncogene suppresser in liver tumor. Next, we did luciferase assay experiment in Huh-7cell to test the p21promoter reporter activity, as a result, we found JMJD2A and p53neither synergistically activated p21nor inhibited it. Luckily, we found it was p27not p21that was up-regulated when JMJD2A was transiently expressed in Huh-7cell. Consistent with that, stably knock down JMJD2A in HepG2cell could decrease the expression of p27and increase cyclinB1significantly. These two results convinced us to believe JMJD2A is an oncogene suppresser in liver carcinoma. We also discovered the new abilities of JMJD2A to assist regulation in transcriptional level:it could interact with β-catenin and assisted its transcription activity, it as well promoted CAR transcription activity. Besides, we found knock down of GCN5could decrease the expression of JMJD2A. This provides a new sight into the interrelationship among different histone modification enzymes.
Keywords/Search Tags:JMJD2A, Liver cancer, Transcriptional regulation
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