Upregulation of miR-196a and HOTAIR Drive Malignant Character in Gastrointestinal Stromal Tumors
Upregulation of miR-196a and HOTAIR Drive Malignant Character in Gastrointestinal Stromal Tumors
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DOI：
10.1158/0008-5472.can-11-1803
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发表时间：
2012-03-01
期刊：
影响因子：
11.2
通讯作者：
Shinomura, Yasuhisa
中科院分区：
文献类型：
--
作者：
Niinuma, Takeshi;Suzuki, Hiromu;Shinomura, Yasuhisa
大型基因间非编码rna （lincRNA）在癌症中的研究少于mirna，尽管两者都具有相当大的治疗潜力。在这项研究中，我们发现miR-196a和lincRNA HOTAIR在高危胃肠道间质瘤（GIST）中频繁上调。在GIST标本中，miR-196a的过表达与高危等级、转移和低生存率相关。miR-196a基因位于HOX基因簇内，微阵列表达分析显示，hoxx和HOTAIR基因在过表达miR-196a的gist中也协同上调。同样，HOTAIR的过表达也与GIST标本的高危等级和转移密切相关。RNA干扰介导的HOTAIR敲低改变了HOTAIR靶基因的表达，抑制了GIST细胞的侵袭性。这些发现揭示了在这种情况下，人类癌症中HOX基因与非编码rna同时过表达，揭示了miR-196a和HOTAIR可能是恶性gist中有用的生物标志物和治疗靶点。癌症Res;72 (5);1126 - 36。(c) 2012年aacr。
Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXCand HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs. Cancer Res; 72(5); 1126-36. (C) 2012 AACR.