Expression of Hqk encoding a KH RNA binding protein is altered in human glioma.

Expression of Hqk encoding a KH RNA binding protein is altered in human glioma.
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DOI:
10.1111/j.1349-7006.2002.tb01255.x
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发表时间:
2002-03
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Abe K
Abe K
中科院分区:
其他
文献类型:
--
作者:
Li ZZ;Kondo T;Murata T;Ebersole TA;Nishi T;Tada K;Ushio Y;Yamamura K;Abe K

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quaking基因家族编码在细胞分化、增殖和凋亡过程中起重要作用的单KH结构域RNA结合蛋白。人类震颤基因Hqk定位于6 q25-q26,其中细胞遗传学改变与多种人类恶性肿瘤相关,包括神经胶质瘤。为了评估Hqk与人类疾病如神经胶质瘤的可能关系,我们首先分离了Hqk基因,表征了其结构和表达模式,并在原发性肿瘤样品中进行了Hqk的突变分析。Hqk基因包含8个外显子,跨越约200 kb的基因组区域,并产生至少4个可变剪接的转录物,Hqk-5,Hqk-6,Hqk-7和Hqk-7 B,其中Hqk-7在脑中大量表达。原发肿瘤中Hqk的表达变化在胶质瘤中的发生率较高(30%; 6/20),而在其他肿瘤如神经鞘瘤(0/3)和脑膜瘤(0/8)中没有表达。在显示表达改变的肿瘤样品中,两个缺乏所有三种主要转录物,一个仅缺失Hqk-5信息,两个病例中仅缺失Hqk-7信息。因此,我们的研究结果暗示Hqk参与人类神经胶质肿瘤的进展。
The quaking gene family encodes single KH domain RNA‐binding proteins that play vital roles in cell differentiation, proliferation, and apoptotic processes. The human quaking gene, Hqk, maps to 6q25–q26, where cytogenetic alterations associated with a variety of human malignancies, including gliomas have been reported. To assess possible relationships of Hqk with human diseases such as glial tumors, we first isolated the Hqk gene, characterized its structure and expression pattern, and carried out mutational analysis of Hqk in primary tumor samples. The Hqk gene contains 8 exons spanning a ∼200 kb genomic region, and generating at least four alternatively spliced transcripts, Hqk–5, Hqk–6, Hqk–7 and Hqk–7B, of which Hqk–7 is abundantly expressed in brain. Analysis of primary tumors demonstrated a high incidence of expression alterations of Hqk in gliomas (30%; 6/20), but not in other tumors such as schwannomas (0/3), or meningiomas (0/8). Among the tumor samples showing expression alterations, two were devoid of all three major transcripts, one was missing only the Hqk–5 message, and only the Hqk–7 message was absent in two cases. Our results thus imply the involvement of Hqk in human glial tumor progression.
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