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KIAA0510、腱膜蛋白-R 基因的 3'-非翻译区和腱膜蛋白-R 在毛细胞星形细胞瘤中过度表达。

KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas.

机构信息

INSERM U 911, Centre de Recherche en Oncologie et Oncopharmacologie, Angiogenèse, Invasivité et Microenvironnement Tumoral, Université de la Méditerranée Aix-Marseille II, Faculté de Médecine la Timone, Marseille, France.

出版信息

Neuropathol Appl Neurobiol. 2010 Aug;36(5):399-410. doi: 10.1111/j.1365-2990.2010.01074.x. Epub 2010 Feb 25.

Abstract

AIMS

Studying the molecules and signalling pathways regulating glioma invasiveness is a major challenge because these processes determine malignancy, progression, relapse and prognosis. We took advantage of our previous study focused on genes that were critical in tumour invasion to further study here an unknown sequence, referred to as KIAA0510, the chromosomal location of which was 1q25, described as a 5596-bp long mRNA and that we found to be significantly overexpressed in pilocytic astrocytomas compared with glioblastomas.

METHODS AND RESULTS

Using in silico analysis as well as Polymerase chain reaction techniques, we decipher the full genomic characterization of the KIAA0510 sequence and demonstrate that KIAA0510 constitutes the 3'-untranslated region of tenascin-R gene. We have clearly confirmed the overexpression of tenascin-R in pilocytic astrocytomas vs. glioblastomas at mRNA and protein levels. We also analysed a large series of various brain tumours and found that in the group of astrocytic tumours, tenascin-R expression decreased with malignancy, whereas oligodendrogliomas sometimes retained a high level of tenascin-R even in high-grade tumours. Gangliogliomas strongly expressed tenascin-R too. In contrast, ependymomas and meningiomas were negative. In normal brain, tenascin-R was exclusively expressed by normal oligodendrocytes and subsets of neurones during post-natal development and in adulthood, where it could differentially affect cellular adhesiveness and/or differentiation.

CONCLUSION

KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas. Gangliogliomas shared with pilocytic astrocytomas strong tenascin-R expression. Whether tenascin-R overexpression negatively influences brain invasion remains to be determined.

摘要

目的

研究调控神经胶质瘤侵袭性的分子和信号通路是一个重大挑战,因为这些过程决定了恶性程度、进展、复发和预后。我们利用之前专注于肿瘤侵袭关键基因的研究,进一步研究了一个未知序列,称为 KIAA0510,其染色体位置位于 1q25,描述为一个长 5596bp 的 mRNA,我们发现它在毛细胞星形细胞瘤中的表达明显高于胶质母细胞瘤。

方法和结果

使用计算机分析和聚合酶链反应技术,我们破译了 KIAA0510 序列的全基因组特征,并证实 KIAA0510 是 tenascin-R 基因的 3'-非翻译区。我们在 mRNA 和蛋白水平上清楚地证实了 tenascin-R 在毛细胞星形细胞瘤与胶质母细胞瘤中的过表达。我们还分析了一系列不同的脑肿瘤,发现在星形细胞瘤组中,tenascin-R 的表达随着恶性程度的增加而降低,而少突胶质细胞瘤在高级别肿瘤中有时仍保持高水平的 tenascin-R。神经节细胞瘤也强烈表达 tenascin-R。相比之下,室管膜瘤和脑膜瘤呈阴性。在正常大脑中,tenascin-R 仅在出生后发育和成年期由正常少突胶质细胞和神经元亚群表达,它可以在细胞黏附和/或分化中发挥不同的作用。

结论

KIAA0510 是 tenascin-R 基因的 3'-非翻译区,tenascin-R 在毛细胞星形细胞瘤中过表达。神经节细胞瘤与毛细胞星形细胞瘤一样强烈表达 tenascin-R。tenascin-R 的过表达是否会对大脑侵袭产生负面影响还有待确定。

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