Abstract
Background: STMN1 is highly expressed in gastric cancer (GC) tissues and the aim of this study was to investigate the role of STMN1 in GC cell stemness. Methods: Analysis of the expression and correlation of STMN1 and its target genes in GC through bioinformatics. Construction of interference plasmids for STMN1 and transfection into GC cells. Sphere formation assay was conducted to detect stem cell sphere-forming ability. WB analysis was performed to detect the expression of stemness genes CD133, ALDH1, CD44, SOX2, Nanog, and STAT3-related proteins. Additionally, CCK-8 assay and TUNEL staining were used to assess GC cell sensitivity to cisplatin (DDP). Construction of a xenograft mouse model to detect the in vivo tumorigenic ability of GC cells. Immunoprecipitation (IP) experiment was conducted to validate the binding of STMN1 and HN1L in GC cells. Overexpression plasmids of HN1L were used for mechanism validation. Results: STMN1 and its target HN1L were highly expressed in GC tissues and cells, and were associated with a poor prognosis in GC. Interfering with STMN1 significantly reduced the self-renewal ability of GC cells, downregulated the expression of CD133, ALDH1, CD44, SOX2, Nanog, p-STAT3 and PD-L1. Interfering with STMN1 increased the sensitivity of GC cells to DDP and promoted apoptosis. IP experiments demonstrate that STMN1 and HN1L combine in GC cells. Overexpression of HN1L significantly reversed the effects of Si-STMN1 on GC cells. In vivo experiments demonstrate that the addition of DDP or interference with STMN1 reduced tumor size and weight, and downregulated the expression of CD133, KI67, HN1L, p-STAT3, and PD-L1 in tumor tissues. The combined use of DPP and Si-STMN1 had a more significant effect. Conclusion: STMN1 regulates GC cell stemness by binding HN1L to activate the HN1L/STAT3/ PD-L1 signaling pathway.