Yang Ye, He Runze, Li Dongxiao, Mu Tianli, Kuang Ziteng, Wang Min
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Cell Biol Toxicol. 2024 Nov 19;40(1):100. doi: 10.1007/s10565-024-09938-6.
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.
锌指蛋白384(ZNF384)是一个与多种肿瘤发生发展相关的高度保守的转录基因,然而,其在浆液性卵巢癌(SOC)中的作用及机制尚不清楚。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ZNF384过表达或敲低细胞系,并通过一系列细胞功能实验,逐步验证ZNF384促进了SOC细胞增殖、迁移和侵袭等一系列恶性行为。通过在裸鼠中建立异种移植模型,证实ZNF384在体内促进了SOC的进展。机制上,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可调节SOC细胞中下游因子泛素D(UBD)的表达,进一步促进SOC的发展。本研究表明,ZNF384通过LIN28B/UBD轴加重了SOC细胞的恶性行为,这可能作为SOC患者的诊断生物标志物。