KIF4A enhanced cell proliferation and migration via Hippo signaling and predicted a poor prognosis in esophageal squamous cell carcinoma

Abstract

Background: In this study, we aimed to explore and clarify the function of KIF4A in esophageal squamous cell carcinoma (ESCC).

Methods: The microarray data were extracted from the Gene Expression Omnibus (GEO) database. We then used the database for Annotation, Visualization, and Integrated Discovery (DAVID) to perform the gene ontology function (GO) and KEGG Orthology-Based Annotation System (KOBAS) to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs). The six core candidate genes were identified using protein-protein interaction (PPI) network analysis and Cytoscape software. Among them, the expression of KIF4A were validated by UALCAN database from the Cancer Genome Atlas (TCGA) (P < 0.05). Western blotting, qRT-PCR and IHC were used to detect the expression of KIF4A in tissues. Cell experiments (transwell migration assays, wound healing assay, CCK8 assay, and clone formation experiment) were utilized to verify the roles of KIF4A on the ESCC cells. Western blotting was used to explore the mechanism of KIF4A in ESCC.

Results: The expression level of KIF4A was upregulated in ESCC samples compared to those in paracancerous tissues. Transwell migration and wound healing assay showed overexpression of KIF4A significantly promoted the migration of ESCC cells. CCK8 assay and clone formation experiment analysis showed that overexpression of KIF4A promoted proliferation of ESCC cells. Western blot detection found that KIF4A could affect the phosphorylation level of Hippo signaling pathway related proteins.

Conclusions: In summary, KIF4A promotes ESCC cell proliferation and migration by regulating the biological function of ESCC cells through the Hippo signaling pathway.

Key points: SIGNIFICANT FINDINGS OF THE STUDY: We found that high KIF4A expression was associated with poor overall survival in esophageal squamous cell carcinoma. KIF4A expression also promoted the proliferation and migration of ESCC cells in vitro.

What this study adds: Our experimental results explain the role of KIF4A in ESCC, and provide a new biomolecular target for the treatment of ESCC.

Keywords: Biomarker; KIF4A; esophageal squamous cell carcinoma; potential biological functions; prognosis.