Mechanism of brain tumor development by neuronal differentiation fail

神经元分化失败导致脑肿瘤发展的机制

基本信息

批准号：
22790347
负责人：
SHIBAZAKI Masahiko
金额：
$ 2.5万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790347/
关键词：
分子病理脳腫瘍 β-TrCP 悪性度神経幹細胞分化異常

项目摘要

(1) The expression ofβIII-tubulin is generally restricted to neurons, but its mRNA is often expressed at a low level in non-neuronal cells. Here, we present evidence thatβIII-tubulin expression occurs in a cell cycle-dependent manner. Both mRNA and protein ofβIII-tubulin accumulated around the G2/M stage of the cell cycle. Furthermore, the cell cycle-dependent expression ofβIII-tubulin was mediated by the neural-restrictive silencing factor NRSF/REST through its binding to the NRSE/RE-1 element that is present in the first intron of theβIII-tubulin gene. These results demonstrate a novel role ofβIII-tubulin in cell cycle progression in tumor cells.(2) Post-transcriptional acetylation-modification of cortactin(CTTN) via the nucleus accumbens-associated 1(NACC1)-histone deacetylase 6(HDAC6) deacetylation system were investigated. The acetylation status of CTTN modulated by the NACC1-HDAC6 deacetylation system induces acceleration of cell migration activity via an actin-dependent cellular process, possibly contributing to aggressive behavior(invasion/metastasis) of the tumor cells.(3) MicroRNAs(miRNAs) are small non-coding RNAs whose aberrations are involved in the initiation and progression of human cancers. We focused on one commonly downregulated miRNA(miR-211), and analyzed its relationship to the expression of preferentially expressed antigen of melanoma(PRAME) protein, which is a potential target of miR-211.These results suggest that downregulation of miR-211 may be partly involved in aberrant expression of the PRAME protein in melanoma cells.

（1）βIII-微管蛋白的表达通常仅限于神经元，但其mRNA通常在非神经元细胞中以低水平表达。在这里，我们提供了证据表明βIII-微管蛋白表达以细胞周期依赖性方式发生。 βIII-微管蛋白的mRNA和蛋白在细胞周期的G2/m阶段获得。此外，神经限制性沉默的沉默因子NRSF/REST通过其与NRSE/RE-1元素的结合介导了βIII-微管蛋白的细胞周期依赖性表达，并通过其与NRSE/RE-1元素结合，该元素在βIIII-Tubulin基因的第一个内含子中介导。这些结果表明，βIII-微管蛋白在肿瘤细胞中细胞周期进展中起了新作用。（2）通过Acumbens相关的1（NACC1） - 组蛋白脱乙酰基酶6（HDAC6）脱乙酰化系统的转录后乙酰化乙酰化 - 乙酰化 - CTTN（CTTN）的作用。 NACC1-HDAC6脱乙酰基化系统调节CTTN的乙酰化状态可通过依赖肌动蛋白依赖性细胞过程诱导细胞迁移活性的加速，这可能导致肿瘤细胞的攻击行为（入侵/转移）。（3）microRNAS（mirNAS）是小型人类rn的cons and and rnaS can and and and can can and in consectiation and can contivation and in contiation and in and can in abereration and in the and in contiation。我们专注于一种通常下调的miRNA（miR-211），并分析了其与优先表达的黑色素瘤抗原（PRAME）蛋白的关系，这是miR-211的潜在靶标。这些结果表明，miR-211的下调可能部分参与黑色素瘤细胞中的蛋白质蛋白的异常表达。