The role of FBXO32 in regulating the growth of esophageal cancer

Abstract

Abstract Purpose Esophageal cancer (EC) is a common and serious form of cancer. F-box protein 32 (FBXO32) is a member of the F-box protein family and its role in EC is still unclear. Methods FBXO32 expression was examined in EC cells using GSE163735 dataset and RT-qPCR and its effects on cell proliferation, migration, and invasion and epithelial mesenchymal transition (EMT) was investigated. The xenograft model established by injecting EC cells transfected with FBX032 was used to evaluate tumor cells growth, apoptosis, proliferation, and metastasis. ChIP assay was employed to study the interaction between FBXO32 with and DNA methyltransferase-1 (DNMT1). Finally, HitPredict, Co-IP, and GST pulldown assay was utilized to analyze the interaction between FBXO32 and CDK9. Results High FBXO32 expression was associated with better overall survival in patients. It is negatively regulated by DNMT1 in EC cells. DNMT1 bound to the FBXO32 promoter to promote its methylationand downregulation in EC cells. Knockdown of DNMT1 in these cells increased FBXO32 expression and suppressed malignant phenotypes. Mechanistically, FBXO32 ubiquitinated and degraded CDK9 (Cyclin Dependent Kinase 9) in EC cells which was prevented in FBXO32-silenced cells. Finally, EC cells overexpressed with FBXO32 inhibited tumor growth and metastasis in xenografts demonstrating its tumor suppressor role. Conclusion FBXO32 is a tumor suppressor that ubiquitinates and degrades CDK9 that results in inhibition of EC.