Oncogenic zinc finger protein ZNF687 accelerates lung adenocarcinoma cell proliferation and tumor progression by activating the PI3K/AKT signaling pathway.

ABSTRACT

BACKGROUND: Zinc finger protein 687 (ZNF687) has previously been discovered as a potential oncogene in individuals with giant cell tumors of the bone, acute myeloid leukemia, and hepatocellular carcinoma. However, its role and mechanism in lung adenocarcinoma (LUAD) remain unclear. METHODS: In LUAD cells, tumor, and matched adjacent tissue specimens, quantitative real-time RT- polymerase chain reaction (qRT-PCR), western blotting analyses, and immunohistochemistry staining (IHC) were conducted. Cell counting kit-8 (CCK8) assay, clonogenicity analysis, flow cytometry, and transwell assays were utilized to detect ZNF687 overexpression and knockdown impacts on cell growth, colony formation, cell cycle, migration, and invasion. Bioinformatic studies, qRT-PCR and western blotting studies were employed to validate the underlying mechanisms and signaling pathways implicated in the oncogenic effect of ZNF687. RESULTS: This study demonstrated that ZNF687 expression was elevated in LUAD cells and tissues. Individuals with upregulated ZNF687 had a poorer prognosis than those with downregulatedZNF687 (p < 0.001). ZNF687 overexpression enhanced LUAD growth, migration, invasion and colony formation, and the cell cycle G1-S transition; additionally, it promoted the epithelial-mesenchymal transition (EMT). In contrast, knocking down ZNF687 showed to have the opposite impact. Moreover, these effects were associated with the activity of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling mechanism. CONCLUSION: ZNF687 was upregulated in LUAD, and high ZNF687 expression levels are associated with poor prognoses. The activation of the PI3K/AKT signaling pathway by upregulated ZNF687 increased the proliferation of LUAD cells and tumor progression. ZNF687 may be a beneficial predictive marker and a therapeutic target in LUAD.