ZNF146 regulates cell cycle progression via TFDP1 and DEPDC1B in ovarian cancer cells

IF 3.7 3区 生物学 Q1 DEVELOPMENTAL BIOLOGY Reproduction Pub Date : 2024-04-01 DOI:10.1530/rep-23-0484
Ruixue Zhao, Nana Song, Xin Ning, Xihai Chen, Rong Ma
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Abstract

Abstract

Ovarian cancer (OC) is the third most common kind of gynecological tumor, in addition to being the most lethal. Transcription factor Dp-1 (TFDP1) functions as a binding partner for E2F transcription factors, and its target genes include those involved in DNA synthesis, cell cycle, and apoptosis. However, the regulatory role of TFDP1 in OC remains incompletely understood. This study aimed to investigate the role and mechanism of TFDP1 in OC. TFDP1 was highly expressed in the ovarian epithelial tissues of OC patients, and the expression of TFDP1 in OC cells was higher than that in normal ovarian epithelial cells. Silencing of TFDP1 inhibited the biological activity of OC cells and hindered cell cycle entry. Zinc finger protein 146 (ZNF146) knockdown induced cell cycle arrest at the G0/G1 phase and tumor growth by blocking TFDP1 transcription, which was overturned by ectopic expression of TFDP1. TFDP1 stimulated DEP domain-containing protein 1B (DEPDC1B) expression through transcriptional activation. DEPDC1B increased the proportion of OC cells in the G2/M phase and potentiated tumor malignant progression in nude mice inhibited by sh-ZNF146. Taken together, these findings demonstrate that ZNF146 participates in TFDP1/DEPDC1B activation and plays a vital role in the cell cycle in OC.

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ZNF146 通过 TFDP1 和 DEPDC1B 调节卵巢癌细胞的细胞周期进展
摘要 卵巢癌(OC)是第三大最常见的妇科肿瘤,也是致死率最高的肿瘤。转录因子Dp-1(TFDP1)是E2F转录因子的结合伙伴,其靶基因包括参与DNA合成、细胞周期和细胞凋亡的基因。然而,TFDP1在OC中的调控作用仍不完全清楚。本研究旨在探讨TFDP1在OC中的作用和机制。TFDP1在OC患者的卵巢上皮组织中高表达,且在OC细胞中的表达高于正常卵巢上皮细胞。TFDP1的沉默抑制了OC细胞的生物活性,阻碍了细胞周期的进入。锌指蛋白146(ZNF146)敲除通过阻断TFDP1的转录诱导细胞周期停滞在G0/G1期和肿瘤生长,而TFDP1的异位表达则推翻了这一结果。TFDP1通过转录激活刺激含DEP结构域蛋白1B(DEPDC1B)的表达。DEPDC1B 增加了处于 G2/M 期的 OC 细胞比例,并增强了 sh-ZNF146 对裸鼠肿瘤恶性进展的抑制作用。综上所述,这些研究结果表明 ZNF146 参与了 TFDP1/DEPDC1B 的激活,并在 OC 的细胞周期中发挥了重要作用。
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来源期刊
Reproduction
Reproduction 生物-发育生物学
CiteScore
7.40
自引率
2.60%
发文量
199
审稿时长
4-8 weeks
期刊介绍: Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.
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