ZNF703 promotes tumor cell proliferation and invasion and predicts poor prognosis in patients with colorectal cancer.

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.