Department of Surgery, Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China.
Cancer Lett. 2012 Jan 28;314(2):223-31. doi: 10.1016/j.canlet.2011.09.033. Epub 2011 Oct 5.
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.
Np95 ICBP90 RING 指（NIRF）对于细胞增殖的调节至关重要，并且与肿瘤发生有关。然而，NIRF 在结直肠癌（CRC）中的作用尚不清楚。在这项研究中，我们证明了 NIRF 在 CRC 组织中的表达异常增加，并且与整体生存不良相关。生物信息学分析表明，NIRF 是 microRNA let-7a 的一个假定靶点，该靶点通过荧光素酶报告基因检测得到证实。然后，我们在体外证明，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 G0/G1 期和细胞迁移减少所致。最后，裸鼠体内致瘤性试验表明，合成 let-7a 抑制 NIRF 的表达并降低肿瘤生长。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。这为针对 NIRF 和 let-7a 进行 CRC 治疗提供了可能性。
