Nicotinamide Phosphoribosyl Transferase (Nampt) Is a Target of MicroRNA-26b in Colorectal Cancer Cells |
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| Authors: | Chenpeng Zhang Jinlu Tong Gang Huang |
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| Affiliation: | 1. Department of Nuclear Medicine, Ren Ji hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, China.; 2. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.; 3. Department of Gastroenterology, Shanghai Institute of Gastrointestinal Diseases; Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; Vanderbilt University Medical Center, United States of America, |
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| Abstract: | 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. |
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