Abstract：
Zinc-finger proteins are involved in many biological processes. However, the role of Zinc-finger protein 334 (ZNF334) in cervical cancer remains unidentified. This study showed that promoter methylation of ZNF334 was responsible for its reduced expression. ZNF334 suppressed malignant biological behaviors in cervical cancer. Notably, ZNF334 reversed the EMT process both in vitro and in vivo. RNA-seq coupled with bioinformatics analysis caught P3H3 which is upregulated by ZNF334. Dual-luciferase reporter and Chromatin immunoprecipitation assays illustrated that ZNF334 directly regulate P3H3. Knockdown of P3H3 attenuated the reversal of EMT induced by ZNF334. Additionally, ZNF334 overexpression sensitized cervical cancer cells to the cytotoxic effects of paclitaxel, cyclosporine and sunitinib. In conclusions, this study illustrated that DNA methylation-based silencing ZNF334 played a vital role in cervical cancer, by regulating P3H3 in turn affects EMT. ZNF334 has the potential to become a novel diagnostic biomarker and a potential treatment target for cervical cancer.
摘要：
锌指蛋白参与许多生物过程。然而,锌指蛋白334(ZNF334)在宫颈癌中的作用尚不明确.这项研究表明ZNF334的启动子甲基化是其表达降低的原因。ZNF334抑制宫颈癌的恶性生物学行为。值得注意的是,ZNF334在体外和体内都逆转了EMT过程。结合生物信息学分析的RNA-seq捕获了由ZNF334上调的P3H3。双荧光素酶报告基因和染色质免疫沉淀测定表明ZNF334直接调节P3H3。P3H3的敲低减弱了由ZNF334诱导的EMT的逆转。此外,ZNF334过表达使宫颈癌细胞对紫杉醇的细胞毒作用敏感,环孢菌素和舒尼替尼。在结论中，这项研究表明，基于DNA甲基化的沉默ZNF334在宫颈癌中起着至关重要的作用，通过调节P3H3反过来影响EMT。ZNF334有潜力成为宫颈癌的新型诊断生物标志物和潜在治疗靶标。
