DKK3与宫颈癌的相关性研究进展

宫颈癌是常见的妇科恶性肿瘤,其发病率和死亡率均较高。DKK3（dickkopf-3）是经典Wnt信号传导通路的拮抗因子,也是近年来发现的抑癌基因。DKK3通过调节β-catenin信号传导通路、逆转上皮-间质转化、抑制肿瘤血管生成等多种途径发挥抗肿瘤功能,是肿瘤治疗中的潜在靶点。基因的表观遗传修饰特别是启动子甲基化在多种恶性肿瘤的发生发展中发挥着非常重要的作用。DKK3基因启动子区的高甲基化是DKK3蛋白失活的重要原因,这使Wnt信号通路异常激活,从而导致肿瘤的发生。宫颈癌组织中DKK3表达常下调,且DKK3基因启动子甲基化导致的DKK3表达沉默是宫颈癌中的频发事件。DKK3的甲基化水平及表达水平与宫颈癌患者预后显著相关,有较好的预测作用。因此,深入研究DKK3与宫颈癌间的关系可能为宫颈癌的机制研究、靶向治疗及判断预后提供新的思路。

Research Progress on the Correlation between DKK3 and Cervical Cancer

Cervical cancer is a common gynecological malignant tumor with high morbidity and mortality. DKK3 (dickkopf-3) is an antagonist of the classic Wnt signaling pathway and a tumor suppressor gene discovered in recent years. DKK3 exerts its anti-tumor function by regulating β-catenin signal transduction pathway, reversing epithelial-mesenchymal transition, inhibiting tumor angiogenesis and other pathways. It is a potential target in tumor therapy. Epigenetic modification of genes, especially promoter methylation, plays a very important role in the occurrence and development of a variety of malignant tumors. Hypermethylation in the promoter region of DKK3 gene is an important reason for the inactivation of DKK3 protein, which makes the Wnt signaling pathway abnormally activated, leading to the occurrence of tumors. The expression of DKK3 is often down-regulated in cervical cancer tissues, and the silencing of DKK3 expression caused by the methylation of the gene promoter is a frequent event in cervical cancer. The methylation level and expression level of DKK3 are significantly correlated to the prognosis of patients with cervical cancer, and it has a good predictive effect. Therefore, in-depth study on the relationship between DKK3 and cervical cancer may provide new ideas for the mechanism research, targeted therapy and prognosis judgment of cervical cancer.