Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer. RNA-binding proteins (RBPs) regulate highly dynamic post-transcriptional processes and perform very important biological functions. Although over 1900 RBPs have been identified, most are considered markers of tumor progression, and further information on their general role in PAAD is not known. Here, we report a bioinformatics analysis that identified five hub RBPs and produced a high-value prognostic model based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Among these, the prognostic signature of the double-stranded RNA binding protein Staufen double-stranded RNA () was identified. Firstly, we found that it is a highly expressed critical regulator of PAAD associated with poor clinical outcomes. Accordingly, the knockdown of led to a profound decrease in PAAD cell growth, migration, and invasion and induced apoptosis of PAAD cells. Furthermore, through multiple omics analyses, we identified the key target genes of : Palladin cytoskeletal associated protein (), Heterogeneous nuclear ribonucleoprotein U (), SERPINE1 mRNA Binding Protein 1 (), and DEAD-box polypeptide 3, X-Linked (). Finally, we found that a high expression level of not only helps PAAD evade the immune response but is also related to chemotherapy drug sensitivity, which implies that could serve as a potential target for combinatorial therapy. These findings uncovered a novel role for in PAAD aggression and resistance, suggesting that it probably represents a novel therapeutic and drug development target.