ZNF862 induces cytostasis and apoptosis via the p21-RB1 and Bcl-xL-Caspase 3 signaling pathways in human gingival fibroblasts

IF 3.4 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of periodontal research Pub Date : 2024-03-14 DOI:10.1111/jre.13250

Yaoyao Zhu, Tian Zhao, Yongkang Wu, Sijing Xie, Weibin Sun, Juan Wu

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Abstract

Objective

This study investigates the effects of ZNF862 on the proliferation and apoptosis of human gingival fibroblasts and their related mechanisms.

Background

As a major transcription factor family, zinc finger proteins (ZFPs) regulate cell differentiation, growth, and apoptosis through their conserved zinc finger motifs, which allow high flexibility and specificity in gene regulation. In our previous study, ZNF862 mutation was associated with hereditary gingival fibromatosis. Nevertheless, little is known about the biological function of ZNF862. Therefore, this study was aimed to reveal intracellular localization of ZNF862, the influence of ZNF862 on the growth and apoptosis of human gingival fibroblasts (HGFs) and its potential related mechanisms.

Methods

Immunohistochemistry, immunofluorescence staining, and western blotting were performed to determine the intracellular localization of ZNF862 in HGFs. HGFs were divided into three groups: ZNF862 overexpression group, ZNF862 interference group, and the empty vector control group. Then, the effects of ZNF862 on cell proliferation, migration, cell cycle, and apoptosis were evaluated. qRT-PCR and western blotting were performed to further explore the mechanism related to the proliferation and apoptosis of HGFs.

Results

ZNF862 was found to be localized in the cytoplasm of HGFs. In vitro experiments revealed that ZNF862 overexpression inhibited HGFs proliferation and migration, induced cell cycle arrest at the G0/G1-phase and apoptosis. Whereas, ZNF862 knockdown promoted HGFs proliferation and migration, accelerated the transition from the G0/G1 phase into the S and G2/M phase and inhibited cell apoptosis. Mechanistically, the effects of ZNF862 on HGFs proliferation and apoptosis were noted to be dependent on inhibiting the cyclin-dependent kinase inhibitor 1A (p21)-retinoblastoma 1 (RB1) signaling pathway and enhancing the B-cell lymphoma-extra-large (Bcl-xL)-Caspase 3 signaling pathway.

Conclusion

Our results for the first time reveal that ZNF862 is localized in the cytoplasm of HGFs. ZNF862 can inhibit the proliferation of HGFs by inhibiting the p21-RB1 signaling pathway, and it also promotes the apoptosis of HGFs by enhancing the Bcl-xL-Caspase 3 signaling pathway.

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ZNF862通过p21-RB1和Bcl-xL-Caspase 3信号通路诱导人牙龈成纤维细胞的细胞凋亡。

研究目的本研究探讨了ZNF862对人牙龈成纤维细胞增殖和凋亡的影响及其相关机制：背景：作为一个主要的转录因子家族，锌指蛋白（ZFPs）通过其保守的锌指基序调控细胞的分化、生长和凋亡，在基因调控中具有高度的灵活性和特异性。在我们之前的研究中，ZNF862 突变与遗传性牙龈纤维瘤病有关。然而，人们对 ZNF862 的生物学功能知之甚少。因此，本研究旨在揭示 ZNF862 在细胞内的定位、ZNF862 对人牙龈成纤维细胞（HGFs）生长和凋亡的影响及其潜在的相关机制：方法：采用免疫组织化学、免疫荧光染色和免疫印迹法测定 ZNF862 在 HGFs 中的胞内定位。HGFs 被分为三组：ZNF862过表达组、ZNF862干扰组和空载体对照组。然后评估 ZNF862 对细胞增殖、迁移、细胞周期和凋亡的影响，并通过 qRT-PCR 和 Western 印迹进一步探讨与 HGFs 增殖和凋亡相关的机制：结果：研究发现 ZNF862 定位于 HGFs 的细胞质中。体外实验发现，ZNF862过表达会抑制HGFs的增殖和迁移，诱导细胞周期停滞在G0/G1期和凋亡。而敲除 ZNF862 则能促进 HGFs 增殖和迁移，加速细胞从 G0/G1 期向 S 期和 G2/M 期转变，抑制细胞凋亡。从机制上看，ZNF862对HGFs增殖和凋亡的影响依赖于抑制细胞周期蛋白依赖性激酶抑制剂1A（p21）-视网膜母细胞瘤1（RB1）信号通路和增强B细胞淋巴瘤-特大型（Bcl-xL）-Caspase 3信号通路：结论：我们的研究结果首次揭示了 ZNF862 定位于 HGFs 的细胞质中。结论：我们的研究结果首次发现了ZNF862定位于HGFs的细胞质中，ZNF862可以通过抑制p21-RB1信号通路抑制HGFs的增殖，也可以通过增强Bcl-xL-Caspase 3信号通路促进HGFs的凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of periodontal research 医学-牙科与口腔外科

CiteScore

6.90

自引率

5.70%

发文量

103

审稿时长

6-12 weeks

期刊介绍： The Journal of Periodontal Research is an international research periodical the purpose of which is to publish original clinical and basic investigations and review articles concerned with every aspect of periodontology and related sciences. Brief communications (1-3 journal pages) are also accepted and a special effort is made to ensure their rapid publication. Reports of scientific meetings in periodontology and related fields are also published. One volume of six issues is published annually.