The pivotal role of ZNF384: driving the malignant behavior of serous ovarian cancer cells via the LIN28B/UBD axis.

IF 5.3 2区 医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2024-11-19 DOI:10.1007/s10565-024-09938-6
Ye Yang, Runze He, Dongxiao Li, Tianli Mu, Ziteng Kuang, Min Wang
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Abstract

Zinc finger protein 384 (ZNF384) is a highly conserved transcribed gene associated with the development of multiple tumors, however, its role and mechanism in serous ovarian cancer (SOC) are unknown. We first confirmed that ZNF384 was abnormally highly expressed in SOC tissues by bioinformatics analysis and immunohistochemistry. We further used lentivirus packaging and transfection techniques to construct ZNF384 overexpression or knockdown cell lines, and through a series of cell function experiments, gradually verified that ZNF384 promoted a series of malignant behaviors of SOC cell proliferation, migration, and invasion. By establishing a xenotransplantation model in nude mice, it was confirmed that ZNF384 promoted the progress of SOC in vivo. Mechanistically, Overexpression of ZNF384 enhanced the transcriptional activity of Lin-28 homolog B (LIN28B), which promoted the malignant behavior of SOC cells. In addition, LIN28B could regulate the expression of the downstream factor ubiquitin D (UBD) in SOC cells, further promoting the development of SOC. This study shows that ZNF384 aggravates the malignant behavior of SOC cells through the LIN28B/UBD axis, which may be used as a diagnostic biomarker for patients with SOC.

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ZNF384 的关键作用:通过 LIN28B/UBD 轴驱动浆液性卵巢癌细胞的恶性行为。
锌指蛋白384(ZNF384)是一种高度保守的转录基因,与多种肿瘤的发生发展有关,但其在浆液性卵巢癌(SOC)中的作用和机制尚不清楚。我们首先通过生物信息学分析和免疫组化证实 ZNF384 在 SOC 组织中异常高表达。我们进一步利用慢病毒包装和转染技术构建了ZNF384过表达或敲除细胞系,并通过一系列细胞功能实验逐步验证了ZNF384促进SOC细胞增殖、迁移和侵袭等一系列恶性行为。通过建立裸鼠异种移植模型,证实了ZNF384促进了SOC在体内的进展。从机理上讲,ZNF384的过表达增强了Lin-28同源物B(LIN28B)的转录活性,从而促进了SOC细胞的恶性行为。此外,LIN28B 还能调控下游因子泛素 D(UBD)在 SOC 细胞中的表达,进一步促进 SOC 的发展。这项研究表明,ZNF384通过LIN28B/UBD轴加剧了SOC细胞的恶性行为,可用作SOC患者的诊断生物标志物。
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来源期刊
Cell Biology and Toxicology
Cell Biology and Toxicology 生物-毒理学
CiteScore
9.90
自引率
4.90%
发文量
101
审稿时长
>12 weeks
期刊介绍: Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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