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ZNF334 在宫颈癌中的作用:对 EMT 逆转和肿瘤抑制的影响。

Role of ZNF334 in cervical cancer: implications for EMT reversal and tumor suppression.

机构信息

Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China.

出版信息

Med Oncol. 2024 Jul 2;41(8):191. doi: 10.1007/s12032-024-02433-2.

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)在宫颈癌中的作用仍未确定。本研究表明,ZNF334 的启动子甲基化导致其表达降低。ZNF334 抑制宫颈癌中的恶性生物学行为。值得注意的是,ZNF334 在体外和体内均逆转了 EMT 过程。RNA-seq 结合生物信息学分析发现,ZNF334 上调了 P3H3。双荧光素酶报告基因和染色质免疫沉淀实验表明,ZNF334 可直接调控 P3H3。P3H3 的敲低减弱了 ZNF334 诱导的 EMT 逆转。此外,ZNF334 的过表达使宫颈癌细胞对紫杉醇、环孢素和舒尼替尼的细胞毒性作用更加敏感。总之,本研究表明,基于 DNA 甲基化的 ZNF334 沉默在宫颈癌中发挥了重要作用,通过调节 P3H3 进而影响 EMT。ZNF334 有可能成为宫颈癌的新型诊断生物标志物和潜在治疗靶点。

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