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Epigenetic dysregulation in hepatocellular carcinoma: focus on polycomb group proteins
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《医学前沿(英文)》 2013年 第7卷 第2期 页码 231-241 doi: 10.1007/s11684-013-0253-7
Hepatocellular carcinoma (HCC) development is characterized by the presence of epigenetic alterations, including promoter DNA hypermethylation and post-translational modifications of histone, which profoundly affect expression of a wide repertoire of genes critical for cancer development. Emerging data suggest that deregulation of polycomb group (PcG) proteins, which are key chromatin modifiers repressing gene transcription during developmental stage, plays a causative role in oncogenesis. PcG proteins assemble into polycomb repressive complex 1 (PRC1) and polycomb repressive complex 2 (PRC2) to impose the histone H3 lysine 27 trimethylation (H3K27me3) modification for repression. In this review, we will first recapitulate the mechanisms of two key epigenetic pathways: DNA methylation and histone modifications. Specifically, we will focus our discussion on the molecular roles of PcG proteins. Next, we will highlight recent findings on PcG proteins, their clinicopathological implication and their downstream molecular consequence in hepatocarcinogenesis. Last but not least, we will consider the therapeutic potential of targeting enhancer of zeste homolog 2 (EZH2) as a possible treatment for HCC. Improving our understanding on the roles of PcG proteins in hepatocarcinogenesis can benefit the development of epigenetic-based therapy.
关键词: liver cancer epigenetics histone modifications polycomb group proteins enhancer of zeste homolog 2 (EZH2)
Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium
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《医学前沿(英文)》 2016年 第10卷 第3期 页码 330-335 doi: 10.1007/s11684-016-0459-6
The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine N-methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.
关键词: polycomb repressive complex Ezh2 expression inner ear cochlea development
Disabled homolog 2 is required for migration and invasion of prostate cancer cells
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《医学前沿(英文)》 2015年 第9卷 第3期 页码 312-321 doi: 10.1007/s11684-015-0401-3
Disabled homolog 2 (DAB2) is frequently deleted or epigenetically silenced in many human cancer cells. Therefore, DAB2 has always been regarded as a tumor suppressor gene. However, the role of DAB2 in tumor progression and metastasis remains unclear. In this study, DAB2 expression was upregulated along with human prostate cancer (PCa) progression. DAB2overexpression or knockdown effects in LNCaP and PC3 cell lines were verified to address the biological functions of DAB2 in PCa progression and metastasis. LNCaP and PC3 cell lines were generated from human PCa cells with low and high metastatic potentials, respectively. The results showed that DAB2 shRNA knockdown can inhibit the migratory and invasive abilities of PC3 cells, as well as the tumorigenicity, whereas DAB2 overexpression enhanced LNCaP cell migration and invasion. Further investigation showed that DAB2 regulated the cell migration associated genes in PC3 cells, and the differential DAB2 expression between LNCaP and PC3 cells was partly regulated by histone 4 acetylation. Therefore, DAB2 may play an important role in PCa progression and metastasis.
Annett SCHROETER, Tanja ENGELBRECHT, Reinhard H. H. NEUBERT
《化学科学与工程前沿(英文)》 2013年 第7卷 第1期 页码 29-36 doi: 10.1007/s11705-013-1302-0
关键词: nano-structure of the stratum corneum ceramide penetration enhancer model membrane neutron diffraction 2H NMR spectroscopy
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Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction
Annett SCHROETER, Tanja ENGELBRECHT, Reinhard H. H. NEUBERT
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