Facilitates Pancreatic Cancer Progression via -Mediated Suppression.

[OBJECTIVES] Pancreatic cancer (PC) is characterized by poor prognosis due to its limited treatment choices and delayed detection. has been implicated in tumor progression, yet its regulatory hierarchy and functional interplay in PC remain unclear. This study aimed to define the role of in PC progression.

[METHODS] Integrated bioinformatic analyses of TCGA-PAAD and GSE22780 datasets identified candidate hub genes. Prognostic relevance was assessed via Kaplan-Meier and ROC analyses. Functional experiments were performed in PANC-1 and BxPC-3 cells, including qRT-PCR, CCK-8 assay, Western blotting, Transwell assay, and apoptosis assay. Co-immunoprecipitation (Co-IP) was used to verify S100A14-S100A16 interaction. CHX chase and dual-luciferase assays were employed to assess protein stability and transcriptional activity.

[RESULTS] was markedly upregulated in PC tissues and cell lines and identified as a key prognostic gene. Silencing suppressed EMT, proliferation, invasion, and migration, while reversing -mediated p53 inhibition and enhancing apoptosis. Mechanistically, Co-IP assay confirmed the protein interaction between and ; stabilized protein through post-translational modification without transcriptional regulation; the axis reduced protein stability and inhibited its transcriptional activity as well as the downstream expression. Critically, knockdown of abrogated the pro-metastatic phenotype of cancer cells.

[CONCLUSION] This study identifies promotes PC progression by stabilizing and suppressing the tumor-suppressive pathway; knockdown of can reverse the above effects, restore function, and enhance cancer cell apoptosis. Targeting the regulatory axis could represent a promising therapeutic approach for PC.