Engrailed homeobox 1 transcriptional regulation of COL22A1 inhibits nasopharyngeal carcinoma cell senescence through the G1/S phase arrest

EN1 is well known as a transcription factor in other tumours, but its role in NPC is unclear. In this study, we first used bioinformatics to analyse GEO data to obtain the differentially expressed gene EN1, and subsequently verified that EN1 was highly expressed in nasopharyngeal carcinoma cells by tissue microarrays as well as cell lines. Further, we down-regulated the expression of EN1 in cells for RNA sequencing. The analysis of sequencing results using KEGG and GO revealed significant changes in cell proliferation and cycle function after downregulation of EN1. Meanwhile, we found that cells underwent senescence after inhibition of EN1 under electron microscopy and the SA-beta-gal assays. Based on the sequencing results, we verified that EN1 can promote the proliferation and cycle of NPC cells in cell function experiments and animal experiments. To investigate how EN1 affects cell senescence, we found that EN1 transcriptional regulation of COL22A1 regulated cell proliferation and cycle via CDK4/6-cyclin D1-Rb signalling pathway by dual luciferase reporter, Immunoblotting and rescue experiment. Accordingly, we uncovered that EN1 could serve as a target for the regulation of senescence in NPC.

Automated summary

This study identified the high expression of EN1 in nasopharyngeal carcinoma cells and demonstrated its role in promoting cell proliferation and cycle while inhibiting cell senescence. The results also revealed the mechanism by which EN1 regulates cell proliferation and cycle through the COL22A1 and CDK4/6-cyclin D1-Rb signaling pathway. These findings highlight the significance of EN1 in regulating senescence in nasopharyngeal carcinoma.