The Tumor-Suppressive Role of SAT2 in Pancreatic Cancer: Involvement in PI3K/Akt-MAPK Pathways and Immune Modulation.

Spermidine/spermine N1-Acetyltransferase 2 (SAT2), belonging to the spermidine/spermine N1-Acetyltransferase family, has been increasingly recognized for its potential effects on tumor occurrence and development. Nonetheless, little is known about its biological function and clinical value for pancreatic cancer (PC). The present work focused on investigating its expression pattern, prognostic value, molecular mechanisms, and immune relevance in PC. SAT2 expression within PC samples and its prognostic significance were analyzed by retrieving the relevant data from the TCGA, CPTAC, and HPA databases. The biological function of SAT2 was investigated through GO and KEGG enrichment analyses. The association of SAT2 with immune cell infiltration in tumors was assessed by CIBERSORT. Additionally, in vitro experiments were performed to examine how SAT2 expression affected the PC cell proliferation, invasion, and migration abilities. An in vivo xenograft tumor model was employed for investigating how SAT2 expression affected the PC cell-derived tumor growth. The expression of SAT2 within the PC tissue exhibited a significant decrease in comparison with a non-carcinoma sample. Such observation was validated within PC cells. In addition, SAT2 expression showed a close relation to both tumor growth (T stage) and prognosis. SAT2 primarily participates in pathways, including the PI3K/Akt and MAPK pathways. Furthermore, we demonstrated a significant association between SAT2 expression and immune cell infiltration into tumors. The in vitro experiments confirmed that elevated SAT2 expression significantly suppressed PC cell viability, invasion, and migration through modulating the PI3K/Akt and MAPK pathways. The in vivo experimental results suggested the role of SAT2 overexpression in inhibiting xenograft tumor growth. Our investigation confirms the role of SAT2 in PC development through involvement in the PI3K/Akt and MAPK pathways. The correlation between SAT2 expression levels, immune infiltration, and checkpoint regulation provides valuable insights for immunotherapy strategies targeting PC.