ZNF677 inhibits oral squamous cell carcinoma growth and tumor stemness by regulating FOXO3a.

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.