Hao Tengfei, Xu Jiannan, Fang Sufen, Jiang Jianlong, Chen Xinyuan, Wu Wenhui, Li Liang, Li Mingzhe, Zhang Changhua, He Yulong
Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China.
J Cancer. 2021 Apr 2;12(11):3198-3208. doi: 10.7150/jca.55079. eCollection 2021.
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 . 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.
锌指蛋白（ZNFs）是一类含有锌指结构域的蛋白质，它们在肿瘤进展中发挥着重要作用。然而，作为锌指蛋白家族的一员，ZNF460在结肠癌中的作用仍不清楚。在本研究中，我们通过组织免疫组化（IHC）和蛋白质免疫印迹法（WB）发现，与癌旁非癌组织相比，临床结肠癌组织中ZNF460蛋白的表达显著增加。我们还通过生物信息学分析在ZNF460的mRNA和蛋白质水平上证实了这一结果。此外，ZNF460的高表达与侵袭深度增加（P<0.05）、淋巴结转移增加（P<0.05）、远处转移（P<0.05）以及高血清CA19-9水平（P<0.05）相关。ZNF460的高表达预示着结肠癌患者的总生存期（OS）和无复发生存期（RFS）较差。此外，多因素分析显示，ZNF460在OS（风险比[HR]：1.636；95%置信区间[CI]，1.028 - 2.603；P = 0.038）和RFS（HR：2.215；95% CI：1.227 - 3.997；P = 0.008）中均为独立的预后因素。ZNF460的敲低抑制了结肠癌细胞的侵袭和转移。机制上，我们发现ZNF460促进结肠癌细胞中JAK2/STAT3信号通路的激活。综上所述，ZNF460的过表达预示着结肠癌患者生存期较差，并通过JAK2/STAT3信号通路促进转移，可能是结肠癌的一个新的治疗靶点。
