J Cancer 2021; 12(11):3198-3208. doi:10.7150/jca.55079

Research Paper

Overexpression of ZNF460 predicts worse survival and promotes metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer

Tengfei Hao1,2*, Jiannan Xu1,2*, Sufen Fang1, Jianlong Jiang1, Xinyuan Chen1, Wenhui Wu1, Liang Li1, Mingzhe Li1, Changhua Zhang1✉, Yulong He1,2✉

1. Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China.
*These authors have contributed equally to this work.

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Citation:
Hao T, Xu J, Fang S, Jiang J, Chen X, Wu W, Li L, Li M, Zhang C, He Y. Overexpression of ZNF460 predicts worse survival and promotes metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer. J Cancer 2021; 12(11):3198-3208. doi:10.7150/jca.55079. Available from https://www.jcancer.org/v12p3198.htm

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Abstract

Zinc finger proteins (ZNFs) are a class of protein containing zinc finger domains, and they play an important role in tumor progression. However, as a member of the ZNFs family, the effect of ZNF460 in colon cancer remains unclear. In this study, we found that the expression of ZNF460 protein were markedly increased in clinical colon cancer tissues compared with para-cancer non-cancerous tissues by tissue immunohistochemistry (IHC) and western blot (WB). We also confirmed this result at the mRNA and protein levels of ZNF460 through bioinformatics analysis. In addition, high expression of ZNF460 was correlated with increased depth of invasion (P<0.05), increased lymph node metastasis (P<0.05), distant metastasis (P<0.05) and high blood serum CA19-9 level (P<0.05). High expression of ZNF460 predicted poor overall survival (OS) and recurrence free survival (RFS) in patients with colon cancer. Moreover, multivariate analyses revealed that ZNF460 was an independent prognostic factor in both OS (hazard ratio [HR]: 1.636; 95% confidence interval [CI], 1.028-2.603; P = 0.038) and RFS (HR: 2.215; 95% CI: 1.227-3.997; P = 0.008). The knockdown of ZNF460 suppressed the invasion and metastasis of colon cancer cells in vitro. Mechanistically, we revealed that ZNF460 promotes the activation of the JAK2/STAT3 signaling pathway in colon cancer cells. Taken together, overexpression of ZNF460 predicted worse survival and promoted metastasis through JAK2/STAT3 signaling pathway in patient with colon cancer, and could be a novel therapeutic target in colon cancer.

Keywords: ZNF460, colon cancer, prognostic, metastasis, JAK2/STAT3