Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs.

Methods: ZNF471 expression and methylation were detected by reverse-transcription PCR and methylation-specific PCR. The impact and mechanism of ectopic ZNF471 expression in esophageal squamous cell carcinoma (ESCC) cells was evaluated in vitro and in vivo.

Results: We identified a 19q13 KRAB-ZFP, ZNF471, as a methylated target in ESCC. We further found that ZNF471 is significantly downregulated in ESCC tissues compared with adjacent non-cancer tissues, due to its aberrant promoter CpG methylation, and further confirmed by methylation analysis and treatment with demethylation agent. Restoration of ZNF471 expression in silenced ESCC cells significantly altered cell morphology, induced apoptosis and G0/G1 arrest, and inhibited tumor cell colony formation, viability, migration and invasion. Importantly, ZNF471 was found to activate the expression of MAPK10/JNK3 and PCDH family genes, and further enhance MAPK10 signaling and downstream gene expression through binding to the MAPK10/JNK3 promoter.

Conclusion: Our results demonstrate that ZNF471 is an important tumor suppressor and loss of ZNF471 functions hampers MAPK10/JNK3 signaling during esophageal carcinogenesis.

锌指蛋白（ZFP）是哺乳动物中最大的转录因子家族，参与多种生理过程的调控，包括细胞分化，增殖，凋亡和肿瘤转化。大约三分之一的ZFP是与Krüppel相关的盒域（KRAB）-ZFP。

方法：通过逆转录PCR和甲基化特异性PCR检测ZNF471的表达和甲基化。体外和体内评估了异位ZNF471表达在食管鳞状细胞癌（ESCC）细胞中的影响和机制。

结果：我们确定了19q13 KRAB-ZFP ZNF471作为ESCC中的甲基化靶标。我们进一步发现，由于其异常的启动子CpG甲基化，与相邻的非癌组织相比，ZNF471在ESCC组织中显着下调，并通过甲基化分析和脱甲基剂处理进一步证实。在沉默的ESCC细胞中ZNF471表达的恢复显着改变细胞形态，诱导凋亡和G0 / G1停滞，并抑制肿瘤细胞集落形成，存活力，迁移和侵袭。重要的是，发现ZNF471激活MAPK10 / JNK3和PCDH家族基因的表达，并通过与MAPK10 / JNK3结合进一步增强MAPK10信号传导和下游基因表达。 启动子。

结论：我们的结果表明ZNF471是重要的肿瘤抑制因子，在食管癌变过程中ZNF471功能的丧失会阻碍MAPK10 / JNK3信号传导。