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人类脑胶质瘤中致癌基因 KLF6-SV1 转录本表达增加。

Increased expression of the oncogenic KLF6-SV1 transcript in human glioblastoma.

机构信息

University Clermont 1, EA 3846, School of Medicine, Clermont-Ferrand, France.

出版信息

Clin Chem Lab Med. 2010 Aug;48(8):1167-70. doi: 10.1515/CCLM.2010.219.

Abstract

BACKGROUND

Gliomas constitute the vast majority of primary central nervous system tumors in adults. Glioblastoma multiforme (GBM) is the most aggressive form of these primary brain tumors. There is a need to define diagnostic and prognostic markers that may help to distinguish GBM from non-GBM tumors. The Krüppel-like factor 6 (KLF6) gene has recently emerged as a promising candidate. The goal of our study was to determine if there is a link between KLF6 splice variants expression and different grades of gliomas.

METHODS

Fifty-three primary gliomas tumor samples were analyzed using quantitative real-time PCR for the total KLF6, wild-type and alternatively spliced (SV1) KLF6 mRNA.

RESULTS

Compared to the non-GBM group, the GBM group had a 2.2-fold increase in the mean level of total KLF6 mRNA expression. GBM showed a 2.1-fold increase in the KLF6 splicing ratio. In addition, KLF6-SV1 mRNA expression levels were also 2.2-fold higher in the GBM group, suggesting that the increase in the KLF6 splicing ratio was due to increased expression of the KLF6-SV1 oncogenic splice variant.

CONCLUSIONS

Our study demonstrates that quantification of total and spliced forms of KLF6 may provide a new and useful supplementary molecular tool for grading glioma.

摘要

背景

神经胶质瘤构成了成人原发性中枢神经系统肿瘤的绝大多数。多形性胶质母细胞瘤(GBM)是这些原发性脑肿瘤中最具侵袭性的形式。需要定义诊断和预后标志物,以帮助区分 GBM 和非 GBM 肿瘤。Krüppel 样因子 6(KLF6)基因最近成为一个很有前途的候选者。我们研究的目的是确定 KLF6 剪接变异体表达与不同级别神经胶质瘤之间是否存在联系。

方法

使用实时定量 PCR 分析 53 例原发性神经胶质瘤肿瘤样本中的总 KLF6、野生型和选择性剪接(SV1)KLF6 mRNA。

结果

与非 GBM 组相比,GBM 组总 KLF6 mRNA 表达水平平均增加了 2.2 倍。GBM 的 KLF6 剪接率增加了 2.1 倍。此外,GBM 组中 KLF6-SV1 mRNA 表达水平也增加了 2.2 倍,这表明 KLF6 剪接率的增加是由于致癌剪接变异体 KLF6-SV1 的表达增加所致。

结论

我们的研究表明,定量分析 KLF6 的总形式和剪接形式可能为神经胶质瘤分级提供一种新的、有用的分子辅助工具。

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