Nicotinamide Phosphoribosyl Transferase (Nampt) Is a Target of MicroRNA-26b in Colorectal Cancer Cells

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.

Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis

“…S4), it is possible that reduced miR-26 levels in tumors is a secondary consequence of impaired differentiation of tumor epithelial cells. Nevertheless, taken together with our functional data from Apc min/+ mice and previous studies that have demonstrated anti-tumorigenic effects of miR-26 expression in human CRC cell lines (Ma et al 2011;Zhang et al 2013), these data strongly suggest a tumor suppressor role for miR-26 in human colon cancer.…”

“…While previous studies have documented anti-tumorigenic effects of miR-26 expression in CRC cell lines (Ma et al 2011;Zhang et al 2013), the significance of these results has remained unclear, since miRNA profiling studies have inconsistently detected miR-26 down-regulation in human colorectal tumors (Schepeler et al 2008;Schetter et al 2008;Motoyama et al 2009;Ma et al 2011;Gaedcke et al 2012). The cellular heterogeneity of normal and neoplastic intestinal tissue can confound the detection of abnormally expressed genes within tumor epithelial cells, the relevant transformed cell type.…”

The role of visfatin (PBEF/Nampt) in pregnancy complications

“…Based on a large analysis of genes associated with GDM, it was proposed that these genes might be further classified as (a) insulin secretion genes; (b) insulin and insulin signaling genes; (c) lipid and glucose metabolism genes; (d) maturity-onset diabetes of the young (MODY) genes; and (e) other genes (Robitaille and Grant, 2008). Most genetic variants associated with GDM and were significantly associated with a higher risk of GDM (Zhang et al, 2013a(Zhang et al, , 2013b.…”

MicroRNA-26b Inhibits Hepatitis B Virus Transcription and Replication by Targeting the Host Factor CHORDC1 Protein

“…The miR-26b expression is frequently abnormal in tumors, indicating that miR-26b plays a significant role in cancer development (20). The miR-26b level is significantly up-regulated in bladder cancer (21), whereas it is down-regulated in liver cancer (22), colorectal cancer (23), and human breast cancer (24,25). miR-26b could serve as a tumor suppressor in colorectal cancer and in glioma (23,26).…”

“…The miR-26b level is significantly up-regulated in bladder cancer (21), whereas it is down-regulated in liver cancer (22), colorectal cancer (23), and human breast cancer (24,25). miR-26b could serve as a tumor suppressor in colorectal cancer and in glioma (23,26). Chronic HBV infection is one of the main causes of hepatocellular carcinoma (HCC), and many miRNAs have essential roles in liver cancer progression by directly targeting a large number of crucial genes in HCC cells (27).…”