No abstract

Zinc finger protein 703 (ZNF703), identified as an oncogene in luminal B breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. However, the role of ZNF703 in colorectal cancer (CRC) is unknown. We investigated the expression of ZNF703 in paired tumor and corresponding normal tissues using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Immunohistochemistry (IHC) was applied on paraffin-embedded specimens, including 138 CRC tissues, 58 matched normal tissues and 30 paired metastatic lymph node samples. Levels of mRNA (72.72%, 16/22) and ZNF703 protein expression (65.38%, 17/26, respectively) were upregulated in CRC tissues. IHC staining revealed higher expression of ZNF703 in the CRC tissues (68/138, 49.3%) compared with that in the adjacent normal mucosal tissues (4/58, 6.9%) (p<0.001). Moreover, high ZNF703 expression was significantly correlated with tumor size, pathological grading, serosal invasion, lymph node metastasis and AJCC stage. CRC patients with relatively low ZNF703 expression had higher survival rates than those with high ZNF703 expression. In addition, we investigated ZNF703 expression in eight CRC cell lines (LS174T, SW480, HT29, SW620, DLD1, SW1116, LoVo and CaCo-2) in vitro. The highest ZNF703 expression was detected in the LoVo cell line. RNA interference was used to assess the effects of ZNF703 knockdown in LoVo cells. Knockdown of ZNF703 expression inhibited CRC cell proliferation and migration. Collectively, these results reveal that ZNF703 may act as an oncogene in CRC and could be considered as a potential therapeutic target for metastatic CRC.

BackgroundInflammatory bowel disease (IBD) is characterized by disturbance of pro-inflammatory cytokines and anti-inflammatory cytokines. Previous studies have demonstrated the effect of anti-inflammatory cytokines, such as interleukin-10 (IL-10) or IL-4 on IBD, but their data were controversial. This study further investigated the effect of IL-4 (IL-4), IL-10 and their combination on treatment of trinitrobenzenesulfonic acid (TNBS)-induced murine colitis.MethodspcDNA3.0 carrying murine IL-4 or IL-10 cDNA was encapsulated with LipofectAMINE 2000 and intraperitoneally injected into mice with TNBS-induced colitis. The levels of intestinal IL-4 and IL-10 mRNA were confirmed by quantitative-RT-PCR. Inflamed tissues were assessed by histology and expression of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and IL-6.ResultsThe data confirmed that IL-4 or IL-10 over-expression was successfully induced in murine colon tissues after intraperitoneal injection. Injections of IL-4 or IL-10 significantly inhibited TNBS-induced colon tissue damage, disease activity index (DAI) and body weight loss compared to the control mice. Furthermore, expression of IFN-γ, TNF-α and IL-6 was markedly blocked by injections of IL-4 or IL-10 plasmid. However, there was less therapeutic effect in mice injected with the combination of IL-4 and IL-10.ConclusionsThese data suggest that intraperitoneal injection of IL-4 or IL-10 plasmid was a potential strategy in control of TNBS-induced murine colitis, but their combination had less effect.