The Melanoma-Upregulated Long Noncoding RNA SPRY4-IT1 Modulates Apoptosis and Invasion
The Melanoma-Upregulated Long Noncoding RNA SPRY4-IT1 Modulates Apoptosis and Invasion
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DOI：
10.1158/0008-5472.can-10-4460
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发表时间：
2011-06-01
期刊：
影响因子：
11.2
通讯作者：
Perera, Ranjan J.
中科院分区：
文献类型：
--
作者：
Khaitan, Divya;Dinger, Marcel E.;Perera, Ranjan J.
肿瘤相关长非编码RNA(LncRNAs)的识别及其分子和生物学功能的研究对于了解肿瘤的分子生物学及其进展具有重要意义。虽然lncRNAs的功能和调控其表达的机制在很大程度上尚不清楚，但最近的研究开始揭示它们在人类健康和疾病中的重要性。在这里，我们报告，与黑素细胞和角质形成细胞对照相比，一些LncRNAs在黑色素瘤细胞系中差异表达。其中一个lncRNAs SPRY4-IT1(GenBank登录号AK024556)来源于SPRY4基因的一个内含子，并被预测在其二级结构中含有几个长发夹。RNA-FISH分析表明，SPRY4-IT1主要定位于黑色素瘤细胞的细胞质中，而SPRY4-IT1 RNAi敲除导致黑色素瘤细胞生长、分化障碍和更高的凋亡率。SPRY4和SPRY4-IT1在体内的差异表达也被检测到，在30个不同的患者样本中，被分类为原发的原位黑色素瘤、区域转移性黑色素瘤、远处转移性黑色素瘤和结节性转移性黑色素瘤。与黑素细胞相比，SPRY4-IT1在黑色素瘤细胞中的高表达，其在细胞质中的积聚，以及对细胞动力学的影响，包括对SPRY4-IT1过表达的伤口闭合率的增加，表明SPRY4-IT1的高表达可能在人类黑色素瘤的分子病因学中起重要作用。癌症资源；71(11)；3852-62。(C)2011年AACR。
The identification of cancer-associated long noncoding RNAs (lncRNAs) and the investigation of their molecular and biological functions are important to understand the molecular biology of cancer and its progression. Although the functions of lncRNAs and the mechanisms regulating their expression are largely unknown, recent studies are beginning to unravel their importance in human health and disease. Here, we report that a number of lncRNAs are differentially expressed in melanoma cell lines in comparison to melanocytes and keratinocyte controls. One of these lncRNAs, SPRY4-IT1 (GenBank accession ID AK024556), is derived from an intron of the SPRY4 gene and is predicted to contain several long hairpins in its secondary structure. RNA-FISH analysis showed that SPRY4-IT1 is predominantly localized in the cytoplasm of melanoma cells, and SPRY4-IT1 RNAi knockdown results in defects in cell growth, differentiation, and higher rates of apoptosis in melanoma cell lines. Differential expression of both SPRY4 and SPRY4-IT1 was also detected in vivo, in 30 distinct patient samples, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic melanoma. The elevated expression of SPRY4-IT1 in melanoma cells compared to melanocytes, its accumulation in cell cytoplasm, and effects on cell dynamics, including increased rate of wound closure on SPRY4-IT1 overexpression, suggest that the higher expression of SPRY4-IT1 may have an important role in the molecular etiology of human melanoma. Cancer Res; 71(11); 3852-62. (C) 2011 AACR.