LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia.
LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia.
复制标题
LncRNA NALT 与 NOTCH1 的相互作用促进儿童 T 细胞急性淋巴细胞白血病的细胞增殖。
DOI：
10.1038/srep13749
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发表时间：
2015-09-02
影响因子：
4.6
通讯作者：
Fang Y
中科院分区：
文献类型：
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作者：
Wang Y;Wu P;Lin R;Rong L;Xue Y;Fang Y
长链非编码RNA（lncRNA）被认为参与多种恶性肿瘤。基于位置的 lncRNA 和基因机制分析受到高度关注。在本研究中，我们报道了名为NALT的lncRNA，其位于NOTCH1附近100bp内。我们证实，在人类样本中，NALT 的上调与 NOTCH1 相关。通过 CCK8 测定和 EDU 染色，NALT 表达的增加显着促进了细胞系中的细胞增殖。进一步的异种移植肿瘤也表明NALT有生长诱导作用，而GSI可以部分逆转。此外，通过对NALT shRNA处理的T ALL细胞中的侧群细胞进行分选，可以降低SP细胞的百分比，并伴有NOTCH1的下调。 Gal4-λN/BoxB报告系统揭示，位于核内的NALT可以作为转录激活因子发挥作用，引起NOTCH信号通路的激活，经蛋白质印迹证实。综上所述，我们发现NOTCH1的邻居Lnc-RP11-611D20.2（命名为NALT）可以通过顺式调节来调节NOTCH1信号通路。这一发现可能会引发诊断或新型分子定向疗法的类似发展。
Long non-coding RNA (lncRNA) was referred to be participating in various malignant tumors. Location based analysis of the mechanism in lncRNA and genes have been highly focused. In this study, we reported that lncRNA named NALT which was located near NOTCH1 within 100 bp away. We confirmed that up-regulation of NALT associating with NOTCH1 in human samples. Increased expression of NALT dramatically promoted cell proliferation in cell lines via CCK8 assay and EDU stain. Further xenograft tumor also indicated the growth inducing affection of NALT while could be partial reversed by GSI. Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1. Gal4-λN/BoxB reporter system revealed that the nuclear located NALT could function as a transcription activator which caused an activation of NOTCH signal pathway as confirmed by western blot. Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation. This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.