The clinical significance of Zinc finger protein 2 in laryngeal squamous cell carcinoma and its potential mechanism

Backgrand: Laryngeal squamous cell carcinoma (LSCC), which arises from the laryngeal mucosa, is the main type of laryngeal cancer. An influence of Zinc finger protein 2 (ZIC2) expression on the occurrence and progression of LSCC has not been established. We aim to identify the clinical importance of ZIC2 expression in LSCC and to explore its latent potential mechanisms. Methods:In this study, we studied the relationship between protein and mRNA expression of ZIC2 in LSCC and clinical pathological features and prognoses via mining the high-throughput sequencing data from multiple databases and to use immunohistochemistry (IHC) and integrated analysis. Meanwhile the downstream targets of ZIC2 transcription factor were also predicted with ChlP-seq data. The KEGG, GO and PPI analysis were applied to identified the potential mechanism of ZIC2 in LSCC. After constructing ZIC2 stable expression cells, we attempt to disclose an association between ZIC2 and cell cycle and apoptosis with RT-qPCR and Western blot methods. Cell cycle was detected by flow cytometry. Results: A higher ZIC2 expression in LSCC were found in both protein and mRNA level by integrated analysis (standard mean difference, SMD=1.76 (95% CI, 1.34–2.18)). The IHC staining of ZIC2 protein is nuclear in LSCC. Kinesin family member 14 (KIF14) was explored as the potential downstream target gene of ZIC2. ZIC2 has a binding peak before the transcription start site of KIF14 and their expression were positively correlated with each other. The expression of KIF14 was elevated after overexpressing ZIC2. The KEGG analysis revealed that ZIC2 may involve LSCC by cell cycle. Cell cycle testing revealed that in ZIC2 knockdown cells, G1 phase increased while S phase was decreased. After knockdown ZIC2 expression, the expression of P21 was elevated, Bax protein was increased while Bcl2 decreased. The analysis of the summary receiver operating characteristic (sROC) demonstrated that ZIC2 may have potential to become a diagnostic marker for LSCC. Conclusions: In conclusion, up-regulation of ZIC2 may contribute to LSCC pathogenesis in cell cycle pathway and it may target KIF14 in LSCC, but these need further research in the future.