Department of Nuclear Medicine, Ren Ji hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2013 Jul 29;8(7):e69963. doi: 10.1371/journal.pone.0069963. Print 2013.
A number of cancers show increased expression of Nicotinamide phosphoribosyl transferase (Nampt). However, the mechanism through which Nampt is upregulated is unclear. In our study, we found that the Nampt-specific chemical inhibitor FK866 significantly inhibited cell survival and reduced nicotinamide adenine dinucleotide (NAD) levels in LoVo and SW480 cell lines. Bioinformatics analyses suggested that miR-26b targets Nampt mRNA. We identified Nampt as a new target of miR-26b and demonstrated that miR-26b inhibits Nampt expression at the protein and mRNA levels by binding to the Nampt 3'-UTR. Moreover, we found that miR-26b was down regulated in cancer tissues relative to that in adjacent normal tissues in 18 colorectal cancer patients. A statistically significant inverse correlation between miR-26b and Nampt expression was observed in samples from colorectal cancer patients and in 5 colorectal cell lines (HT-29, SW480, SW1116, LoVo, and HCT116). In addition, over expression of miR-26b strongly inhibited LoVo cell survival and invasion, an effect partially abrogated by the addition of NAD. In conclusion, this study demonstrated that the NAD-salvaging biosynthesis pathway involving Nampt might play a role in colorectal cancer cell survival. MiR-26b may serve as a tumor suppressor by targeting Nampt.
许多癌症表现出烟酰胺磷酸核糖转移酶（Nampt）表达增加。然而，Nampt上调的机制尚不清楚。在我们的研究中，我们发现 Nampt 特异性化学抑制剂 FK866 显著抑制 LoVo 和 SW480 细胞系的细胞存活并降低烟酰胺腺嘌呤二核苷酸（NAD）水平。生物信息学分析表明，miR-26b 靶向 Nampt mRNA。我们确定 Nampt 是 miR-26b 的一个新靶标，并证明 miR-26b 通过结合 Nampt 3'-UTR 抑制 Nampt 蛋白和 mRNA 水平的表达。此外，我们发现 18 例结直肠癌患者的癌组织中 miR-26b 的表达相对邻近正常组织下调。在结直肠癌患者和 5 种结直肠细胞系（HT-29、SW480、SW1116、LoVo 和 HCT116）的样本中观察到 miR-26b 和 Nampt 表达之间存在统计学上显著的负相关。此外，miR-26b 的过表达强烈抑制 LoVo 细胞的存活和侵袭，添加 NAD 部分消除了这种作用。总之，本研究表明涉及 Nampt 的 NAD 挽救生物合成途径可能在结直肠癌细胞存活中发挥作用。miR-26b 可能通过靶向 Nampt 作为肿瘤抑制因子发挥作用。
