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RRP22:神经胶质细胞瘤的新型神经肿瘤抑制因子。

RRP22: a novel neural tumor suppressor for astrocytoma.

机构信息

Department of Neurosurgery, Xiangya Hospital of Central South University, 410078 Changsha, Hunan, People's Republic of China.

出版信息

Med Oncol. 2012 Mar;29(1):332-9. doi: 10.1007/s12032-010-9795-6. Epub 2011 Jan 25.

Abstract

Astrocytomas are the most common neoplasm of the central nervous system. Although progress has been made, the survival rate of astrocytoma is still poor. Therefore, improving the prognosis of patients with astrocytomas relies on effective therapies that are directed against unique molecular aberrations. Previous studies have revealed that a novel member of the Ras superfamily, RRP22, which is located on chromosome 22 on the 12q site, is exclusively expressed in the central nervous system. RRP22 can be modified by farnesyl and down-regulated in a variety of neural tumor cell lines. In this study, we analyzed the mRNA level of RRP22 in normal brain tissues and astrocytomas using quantitative RT-PCR. Our results showed that the mRNA level in astrocytomas was significantly down-regulated compared to levels in normal tissues. As the pathological grade (World Health Organization (WHO) classification 2007) increased, the expression of RRP22 decreased. However, according to our research, there was no significant difference between malignant astrocytomas with pathological grades of III or IV. To investigate the possible effects of RRP22 on the biological behavior of glioma cells, we transfected RRP22 into a malignant cell line of astrocytomas, U251. We found that RRP22 inhibited growth, decreased invasiveness, and induced cell death. Thus, RRP22 is a special neural tumor suppressor for human astrocytomas, although further studies are needed to define the detailed mechanisms.

摘要

星形细胞瘤是中枢神经系统最常见的肿瘤。尽管已经取得了进展,但星形细胞瘤的生存率仍然很差。因此,改善星形细胞瘤患者的预后依赖于针对独特分子异常的有效治疗方法。先前的研究表明,位于 22 号染色体 12q 位点上的 Ras 超家族的一个新成员 RRP22 专门在中枢神经系统中表达。RRP22 可以被法呢基化修饰,并在多种神经肿瘤细胞系中下调。在这项研究中,我们使用定量 RT-PCR 分析了正常脑组织和星形细胞瘤中 RRP22 的 mRNA 水平。结果表明,星形细胞瘤中的 mRNA 水平明显低于正常组织。随着病理分级(世界卫生组织 2007 年分类)的增加,RRP22 的表达下降。然而,根据我们的研究,病理分级为 III 或 IV 的恶性星形细胞瘤之间没有显著差异。为了研究 RRP22 对神经胶质瘤细胞生物学行为的可能影响,我们将 RRP22 转染到星形细胞瘤的恶性细胞系 U251 中。结果发现,RRP22 抑制了细胞生长,降低了侵袭性,并诱导了细胞死亡。因此,RRP22 是人类星形细胞瘤的一种特殊的神经肿瘤抑制因子,尽管需要进一步研究来确定其详细的作用机制。

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