The lncRNA ST18-AS1 suppresses pancreatic cancer progression by enhancing ST18 mRNA stability through anchoring FUS in the cytoplasm

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high mortality rate and short survival time. Long noncoding RNAs (lncRNAs) play a significant role in the progression of PDAC. However, prognostic lncRNAs associated with overall survival (OS) in patients with PDAC remain elusive. RNA sequencing was used to identify differential lncRNA expression between short-term and long-term PDAC patients. We identified a novel lncRNA (ENSG00000253924), termed ST18-AS1 (ST18-associated lncRNA), that is highly expressed in the tissues of long-term PDAC patients. High ST18-AS1 expression was correlated with favorable clinical outcomes, and the upregulation of ST18-AS1 expression in PDAC cell lines suppressed cell proliferation and promoted apoptosis both in vivo and in vitro. The key downstream target regulated by ST18-AS1 was Suppression of tumorigenicity 18 (ST18). We also found that ST18 expression was lower in PDAC tissues compared to non-tumorous adjacent tissues (NATs) and that higher ST18 expression was correlated with better clinical outcomes. Accordingly, the forced expression of ST18 inhibited proliferation and promoted apoptosis in tumor cells. Mechanistic studies showed that ST18-AS1 maintained the stability of ST18 mRNA by binding to Fused in sarcoma (FUS) and anchoring FUS in the cytoplasm. Overall, we identified ST18-AS1 as a novel biomarker that inhibits PDAC cell proliferation and promotes PDAC cell apoptosis through ST18. Targeting ST18-AS1/ST18 may be a potential therapeutic strategy for treating PDAC.