Jangravi Zohreh, Najafi Mohammad, Shabani Mohammd
Dept. of Biochemistry, Iran University of Medical Sciences, Tehran, Iran.
Dept. of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Iran Biomed J. 2016;20(2):117-21. doi: 10.7508/ibj.2016.02.007. Epub 2015 Nov 24.
It is now well-demonstrated that histone demethylases play an important role in developmental controls, cell-fate decisions, and a variety of diseases such as cancer. Lysine-specific demethylase 5D (KDM5D) is a male-specific histone demethylase that specifically demethylates di- and tri-methyl H3K4 at the start site of active gene. In this light, the aim of this study was to investigate isoform/transcript-specific expression profiles of KDM5D in three prostate cancer cell lines, Du-145, LNCaP, and PC3.
Real-time PCR analysis was performed to determine the expression levels of different KDM5D transcripts in the prostate cell lines. A gene regulatory network was established to analyze the gene expression profile.
Significantly different expression levels of both isoforms were found among the three cell lines. Interestingly, isoform I was expressed in three cell lines while isoform III did only in DU-145. The expression levels of both isoforms were higher in DU-145 when compared to other cell lines (P<0.0001). The observed expression profile was determined by using regulatory network analyses.
The present study, for the first time, not only showed the expression profiles of KDM5D isoforms in prostate cancer cell lines but also evaluated the effects of the gene regulatory network on the expression profile of this gene.
现已充分证明,组蛋白去甲基化酶在发育控制、细胞命运决定以及多种疾病(如癌症)中发挥重要作用。赖氨酸特异性去甲基化酶5D(KDM5D)是一种雄性特异性组蛋白去甲基化酶,它在活性基因起始位点特异性地使二甲基和三甲基H3K4去甲基化。鉴于此,本研究的目的是调查KDM5D在三种前列腺癌细胞系Du-145、LNCaP和PC3中的异构体/转录本特异性表达谱。
进行实时PCR分析以确定前列腺癌细胞系中不同KDM5D转录本的表达水平。建立基因调控网络以分析基因表达谱。
在这三种细胞系中发现两种异构体的表达水平存在显著差异。有趣的是,异构体I在三种细胞系中均有表达,而异构体III仅在DU-145中表达。与其他细胞系相比,DU-145中两种异构体的表达水平更高(P<0.0001)。通过调控网络分析确定了观察到的表达谱。
本研究首次不仅展示了KDM5D异构体在前列腺癌细胞系中的表达谱,还评估了基因调控网络对该基因表达谱的影响。