锌指蛋白 862 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静止和凋亡。
ZNF862 induces cytostasis and apoptosis via the p21-RB1 and Bcl-xL-Caspase 3 signaling pathways in human gingival fibroblasts.
机构信息
Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
出版信息
J Periodontal Res. 2024 Jun;59(3):599-610. doi: 10.1111/jre.13250. Epub 2024 Mar 14.
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.
目的
本研究旨在探讨 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
锌指蛋白（ZFPs）作为主要的转录因子家族，通过其保守的锌指结构域调节细胞分化、生长和凋亡，从而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，关于 ZNF862 的生物学功能知之甚少。因此，本研究旨在揭示 ZNF862 的细胞内定位，研究 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
采用免疫组化、免疫荧光染色和 Western blot 法检测 ZNF862 在 HGFs 中的细胞内定位。将 HGFs 分为 ZNF862 过表达组、ZNF862 干扰组和空载对照组。然后，评估 ZNF862 对细胞增殖、迁移、细胞周期和凋亡的影响。采用 qRT-PCR 和 Western blot 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。体外实验结果显示，ZNF862 过表达抑制 HGFs 增殖和迁移，诱导细胞周期停滞在 G0/G1 期并促进细胞凋亡。而 ZNF862 敲低则促进 HGFs 增殖和迁移，加速 G0/G1 期向 S 和 G2/M 期的转变，并抑制细胞凋亡。机制上，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-extra-large（Bcl-xL）-Caspase 3 信号通路。
结论
本研究首次揭示 ZNF862 定位于 HGFs 的细胞质中。ZNF862 可通过抑制 p21-RB1 信号通路抑制 HGFs 的增殖，通过增强 Bcl-xL-Caspase 3 信号通路促进 HGFs 的凋亡。
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