NIRF is frequently upregulated in colorectal cancer and its oncogenicity can be suppressed by let-7a microRNA
NIRF is frequently upregulated in colorectal cancer and its oncogenicity can be suppressed by let-7a microRNA
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NIRF 在结直肠癌中经常上调，其致癌性可被 let-7a microRNA 抑制。
DOI：
10.1016/j.canlet.2011.09.033
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发表时间：
2012-01-28
期刊：
影响因子：
9.7
通讯作者：
Qin, Huanlong
中科院分区：
文献类型：
--
作者：
Wang, Feng;Zhang, Peng;Qin, Huanlong
Np 95 ICBP 90环指（NIRF）是调节细胞增殖所必需的，并与肿瘤发生有关。然而，NIRF在结直肠癌（CRC）中的作用仍不清楚。在这项研究中，我们证明了NIRF表达在结直肠癌组织中异常增加，并与总生存率低相关。生物信息学分析表明NIRF是microRNA let-7a的推定靶点，荧光素酶报告基因实验证实了这一点。然后，我们在体外证明了let-7a的强制表达或NIRF的敲低导致CRC细胞增殖减少，这是由于细胞周期停滞在G 0/G1期和细胞迁移减少。最后，裸鼠体内致瘤性试验表明，合成let-7a抑制NIRF表达和减少肿瘤生长。总之，我们的研究结果提供了新的证据表明，NIRF在CRC中具有致癌作用。这开辟了靶向NIRF和let-7a用于CRC治疗的可能性。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Np95 ICBP90 RING finger (NIRF) is essential for the regulation of cell proliferation and has been implicated in tumorigenesis. However, the role of NIRF in colorectal cancer (CRC) remains unclear. In this study, we demonstrated that NIRF expression was aberrantly increased in CRC tissues and associated with poor overall survival. Bioinformatics analysis indicated that NIRF was a putative target of the microRNA let-7a, which was confirmed by luciferase reporter assay. We then demonstrated in vitro that enforced expression of let-7a, or knockdown of NIRF, led to reduced CRC cell proliferation due to cell cycle arrest at the G0/G1 phase and reduced cell migration. Finally, an in vivo tumorigenicity assay in nude mice showed that synthetic let-7a suppressed NIRF expression and reduced tumor growth. Taken together, our results provide new evidence that NIRF has an oncogenic role in CRC. This opens up the possibility of targeting NIRF and let-7a for CRC therapy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.