Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway.
Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway.
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DOI：
10.1186/1476-4598-9-59
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发表时间：
2010-03-13
期刊：
影响因子：
37.3
通讯作者：
Hamamoto R
中科院分区：
文献类型：
--
作者：
Hayami S;Yoshimatsu M;Veerakumarasivam A;Unoki M;Iwai Y;Tsunoda T;Field HI;Kelly JD;Neal DE;Yamaue H;Ponder BA;Nakamura Y;Hamamoto R
尽管已经鉴定出越来越多的组蛋白脱甲基酶并在生化表征中表征了它们，但它们的生物学功能在很大程度上仍然没有表征，尤其是在癌症等人类疾病的背景下。我们研究了JMJC组蛋白脱甲基酶在人癌变中的作用。定量RT-PCR和微阵列分析用于检查临床组织样品中组蛋白脱甲基酶的表达谱。我们还检查了KDM5B对用小型干扰RNA（siRNA）处理的癌细胞系的生长的功能作用。从Affymetrix基因芯片实验中鉴定出由KDM5B表达诱导的下游基因和信号级联反应，并通过实时PCR和报告基因测定验证。通过免疫荧光和FACS鉴定了KDM5B的细胞周期依赖性特征。
定量RT-PCR分析证实，人膀胱癌组织的KDM5B表达水平明显高于其相应的非肿瘤膀胱组织（P <0.0001）。临床组织的表达谱分析还表明，KDM5B在各种恶性肿瘤中上调。将KDM5B特异性siRNA转染到各种膀胱和肺癌细胞系中，显着抑制了癌细胞的增殖，并增加了Sub-G1期细胞的数量。微阵列表达分析表明E2F1和E2F2是KDM5B途径中的下游基因。
KDM5B的抑制可能会影响凋亡并减少癌细胞的生长。进一步的研究将探索KDM5B抑制作用的Pan-Cancer治疗潜力。
Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition.
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影响因子：
10.5
作者：
DEGREGORI, J;LEONE, G;NEVINS, JR
通讯作者：
NEVINS, JR
影响因子：
64.5
作者：
Klose, Robert J.;Yan, Qin;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
影响因子：
8
作者：
Kikuchi, T;Daigo, Y;Nakamura, Y
通讯作者：
Nakamura, Y
影响因子：
7.3
作者：
Gorgoulis, VG;Zacharatos, P;Papavassiliou, AG
通讯作者：
Papavassiliou, AG
影响因子：
16
作者：
Kubicek, Stefan;O'Sullivan, Roderick J.;Jenuwein, Thomas
通讯作者：
Jenuwein, Thomas