ZNF334 在宫颈癌中的作用:对 EMT 逆转和肿瘤抑制的影响

IF 2.8 4区 医学 Q2 ONCOLOGY
Qian Li, Xiangyi Zhou, Jiayi Xiao, Yijia Gong, Xue Gong, Bianfei Shao, Jianhua Wang, Lijuan Zhao, Qi Xiong, Yue Wu, Jun Tang, Qiyu Yang, Junying Tang, Tingxiu Xiang
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引用次数: 0

摘要

锌指蛋白参与了许多生物过程。然而,锌指蛋白 334(ZNF334)在宫颈癌中的作用仍未确定。这项研究表明,ZNF334启动子甲基化是其表达减少的原因。ZNF334抑制了宫颈癌的恶性生物学行为。值得注意的是,ZNF334在体外和体内都能逆转EMT过程。RNA-seq结合生物信息学分析发现了ZNF334上调的P3H3。双荧光素酶报告和染色质免疫沉淀分析表明,ZNF334 直接调控 P3H3。敲除 P3H3 可减轻 ZNF334 诱导的 EMT 的逆转。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敏感。总之,这项研究表明,基于 DNA 甲基化的 ZNF334 沉默在宫颈癌中发挥了重要作用,它通过调节 P3H3 进而影响 EMT。ZNF334有望成为宫颈癌的新型诊断生物标志物和潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
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