Department of Stomatology, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 250, East Street, Quanzhou, 362000, Fujian, China.
Department of Prosthodontics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350000, Fujian, China.
Hum Cell. 2023 Jul;36(4):1464-1476. doi: 10.1007/s13577-023-00910-w. Epub 2023 May 2.
Oral squamous cell carcinoma (OSCC) is a common cancer with an increasing incidence worldwide. Zinc-finger proteins 677 (ZNF677) is involved in the progression and methylation of various cancers, but its role and mechanism in OSCC remain indeterminate. The expression of ZNF677 was analyzed by online database and immunohistochemistry, while the methylation level of ZNF677 was determined by the methylation-specific PCR. The role and mechanism of ZNF677 in the tumor cell growth, migration, invasion and stemness were addressed by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell, wound-healing, sphere‑formation, and western blot assays. In addition, its function was also investigated in a xenografted mice model. The results showed that ZNF677 was lowly expressed in OSCC with a hypermethylation level, which predicted poor overall survival in patients with HNSC. Upregulation of ZNF677 reduced the cell viability, Edu positive cells, numbers of invasion cells, the migration ability, numbers of spheres formation and the expression of proliferation, migration and stemness related proteins in CAL-27 and SCC25 cells. Mechanically, the relative levels of p-AKT/AKT were decreased and the levels of p-FOXO3a/FOXO3a were increased in both cells overexpressed with ZNF677, which were reversed by the SC79 treatment. Moreover, interference of FOXO3a recovered the suppressive effects of ZNF677 overexpression on cell proliferation, migration, invasion and stemness of OSCC cells. Furthermore, overexpression of ZNF677 reduced the tumor volume and weight, and the relative protein level of p-AKT/AKT with an increased level of p-FOXO3a/FOXO3a, and improved pathological symptoms in vivo. Collectively, ZNF677 suppressed OSCC cells growth, migration, invasion and stemness through inhibiting AKT/FOXO3a pathway.
口腔鳞状细胞癌（OSCC）是一种常见的癌症，其发病率在全球范围内呈上升趋势。锌指蛋白 677（ZNF677）参与了多种癌症的进展和甲基化，但它在 OSCC 中的作用和机制仍不确定。通过在线数据库和免疫组织化学分析 ZNF677 的表达，通过甲基化特异性 PCR 确定 ZNF677 的甲基化水平。通过细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）掺入、Transwell、划痕愈合、球体形成和 Western blot 分析研究 ZNF677 在肿瘤细胞生长、迁移、侵袭和干性中的作用和机制。此外，还在异种移植小鼠模型中研究了其功能。结果表明，ZNF677 在 OSCC 中表达较低，甲基化水平较高，预测 HNSC 患者总体生存率较差。ZNF677 的上调降低了 CAL-27 和 SCC25 细胞的细胞活力、EdU 阳性细胞数、侵袭细胞数、迁移能力、球体形成数以及增殖、迁移和干性相关蛋白的表达。在机制上，过表达 ZNF677 的两种细胞中相对 AKT/AKT 的水平降低，而 p-FOXO3a/FOXO3a 的水平升高，这一现象被 SC79 处理所逆转。此外，干扰 FOXO3a 恢复了 ZNF677 过表达对 OSCC 细胞增殖、迁移、侵袭和干性的抑制作用。此外，ZNF677 的过表达降低了肿瘤体积和重量，降低了 AKT/AKT 的相对蛋白水平，增加了 FOXO3a/FOXO3a 的相对蛋白水平，并改善了体内的病理症状。总之，ZNF677 通过抑制 AKT/FOXO3a 通路抑制 OSCC 细胞的生长、迁移、侵袭和干性。
