ZNF488 Enhances the Invasion and Metastasis through Activating the MAPK/ERK Signaling Pathway in Non-Small Cell Lung Cancer

Abstract Background: This study aimed to explore the relationship between zinc finger protein 488 (ZNF488) and non-small cell lung cancer (NSCLC), as well as the function and mechanism of ZNF488 involved in the invasion and metastasis. Method：TCGA and HPA databases were used to analyze NSCLC data. Quantitative Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression level of ZNF488 in tissues. 100 cases of NSCLC tissues were subjected to immunohistochemical staining (IHC) to evaluate the endogenous expression of ZNF488, and than analyze its correlation with clinical characteristics. After constructing ZNF488 stably overexpressing cell lines, wound healing test and transwell invasion assays were used to explore the invasion and migration ability of lung cancer cells in both ZNF488 over-expressing and the vector control cell lines. In vivo, we used ZNF488 over-expressing and the vector control cell lines to construct animal models of lung metastasis by tail vein injection. The gene chip technology was used to explore the differential genes between vector and ZNF488 over-expressing group. The DAVID database was used to analyze the differential genes by KEGG pathway MEK inhibitor AZD6244 was used to verify the potential signaling pathway. Western blot was used to detect the protein expression levels. Results：The expression of ZNF488 in NSCLC tissues was generally higher than that in normal lung tissues, and its expression level was significantly related to TNM stage, overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (p<0.05). The results of functional and animal experiments showed that ZNF488 promoted the cell invasion and matastasis in NSCLC. In terms of mechanism, ZNF488 can induce epithelial-mesenchymal transition (EMT) in NSCLC by activating the MAPK/ERK signaling pathway, thereby promoting the invasion and metastasis. MEK inhibitor AZD6244. could partially reverse ZNF488-induced invasive ability. Conclusion: As an independent prognostic indicator, ZNF488 can promote the invasion and metastasis by activating the MAPK/ERK signaling pathway in NSCLC .