Dihydropyrimidinase-like protein 3 expression is negatively regulated by MYCN and associated with clinical outcome in neuroblastoma.
Dihydropyrimidinase-like protein 3 expression is negatively regulated by MYCN and associated with clinical outcome in neuroblastoma.
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DOI：
10.1111/cas.12278
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发表时间：
2013-12
期刊：
影响因子：
5.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Tan F;Wahdan-Alaswad R;Yan S;Thiele CJ;Li Z
二氢吡啶酶样蛋白（DPYSL）是在神经系统成熟过程中开发和调节的蛋白质家族，据报道DPYSL家族的成员与DPYSL1的癌症相关性低。细胞肺癌和作为转移抑制剂的作用。到目前为止，NB中DPYSL的生物学功能仍然难以捉摸。 ，DPYSL2和DPYSL3，我们调节了它们在NB细胞中RA诱导的分化过程中的表达及其亚细胞分布DPYSL和MYCN是NB预后不良的生物标志物，我们发现DPYSL3水平在RA诱导的细胞分化过程中增加了MYCN的下调。在非Mycn NB细胞中，DPYSL3水平降低了DPYSL1和DPYSL2的表达在RA处理过程中没有变化Mycn的水平。由MYCN，也许用作NB的潜在生物标志物。
Dihydropyrimidinase-like proteins (DPYSLs) are a family of proteins developmentally regulated during maturation of the nervous system. Recently, members of DPYSL family have been reported to be involved in cancer with low expression of DPYSL1 correlating with poor clinical outcomes in non-small cell lung cancer and functioning as a metastasis suppressor. Neuroblastoma (NB) is a tumor derived from precursor cells of the sympathetic nervous system and is the most common solid tumor in childhood. So far the biological functions of DPYSLs in NB remain elusive. Studying the potential roles of DPYSLs in NB may give us new insights into NB tumorigenesis. In the present study, using antibodies specific to different members of the DPYSL family, DPYSL1, DPYSL2 and DPYSL3, we investigated regulation of their expression and their subcellular distribution during RA-induced differentiation in NB cells. The correlation between DPYSLs and MYCN, a biomarker for poor prognosis of NB, was evaluated. We found that DPYSL3 levels increased during RA-induced cell differentiation. Down-regulation of MYCN by small interfering RNA (siRNA) increased DPYSL3 levels, while up-regulation of MYCN in non-MYCN NB cells decreased DPYSL3 levels. DPYSL1 and DPYSL2 expression didn’t change during RA treatment or under different expression levels of MYCN. Moreover, high level of DPYSL3 mRNA, but not that of DPYSL1 or DPYSL2 mRNA, was detected in tumors from advanced-stage NB that have a better survival. These data indicated that DPYSL3, not DPYSL1 or DPYSL2, is negatively regulated by MYCN and maybe used as a potential biomarker for NB.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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