RESUMO
BACKGROUND: Most colorectal cancer (CRC) patients are diagnosed at an advanced or metastatic stage with poor prognosis. Ubiquitin-specific protease 6 N-terminal-like protein (USP6NL) with high expression in CRC tissues regulates CRC cell proliferation via Wnt/ß-catenin pathway. We hypothesized that USP6NL impacts CRC growth and inhibition of USP6NL may be a novel treatment strategy to improve CRC therapy. METHODS: USP6NL level in human CRC tissues and its association with tumor growth and metastasis were examined. Its roles and potential mechanisms in regulating tumor growth were studied by genetic and pharmacological manipulation of CRC cells in vitro and in vivo. RESULTS: Herein, we found that USP6NL was up-regulated in tumorous tissues of CRC patients. Our data suggested that knockdown of USP6NL in human CRC cell lines (HCT116 and LOVO cells) inhibited cell proliferation, induced G0/G1 cell cycle arrest, and prevented the tumorigenicity of HCT116 cells in nude mice, and which was associated with the prevention of Wnt/ß-catenin pathway. On the contrary, USP6NL overexpression in human CRC cells (SW480) showed the opposite result. Our data suggested that the promoted cell proliferation, G1/S cell cycle progression, and the enhanced expression of ß-catenin Cyclin D1 and C-myc while reduced P27 induced by the overexpression of USP6NL were significantly reversed by additional treatment of XAV939, indicating that activating Wnt/ß-catenin pathway was the mechanism, by which USP6NL exerted carcinogenesis in CRC in vitro. Besides, our data suggested that knockdown of USP6NL increased the ubiquitination of ß-catenin, indicating that USP6NL may serve as a deubiquitinase that regulated ß-catenin accumulation in this process. Furthermore, 10058-F4 down-regulated USP6NL, inhibited CRC cell proliferation and induced cell cycle arrest. The result demonstrated a possible feedback loop between USP6NL, ß-catenin and C-myc in regulating CRC cell growth. CONCLUSION: USP6NL was an oncogene in CRC, and it may be a potential target for the treatment of CRC.
RESUMO
The red-crowned crane is one of the rarest crane species, and its population is decreasing due to loss of habitat, poisoning, and infections. Using a viral metagenomics approach, we analyzed the virome of feces from wild and captive red-crowned cranes, which were pooled separately. Vertebrate viruses belonging to the families Picornaviridae, Parvoviridae, Circoviridae, and Caliciviridae were detected. Among the members of the family Picornaviridae, we found three that appear to represent new genera. Six nearly complete genomes from members of the family Parvoviridae were also obtained, including four new members of the proposed genus "Chapparvovirus", and two members of the genus Aveparvovirus. Six small circular DNA genomes were also characterized. One nearly complete genome showing a low level of sequence identity to caliciviruses was also characterized. Numerous viruses believed to infect insects, plants, and crustaceans were also identified, which were probably derived from the diet of red-crowned cranes. This study increases our understanding of the enteric virome of red-crowned cranes and provides a baseline for comparison to those of other birds or following disease outbreaks.