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

Abstract

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 (STAU2) was identified. Firstly, we found that it is a highly expressed critical regulator of PAAD associated with poor clinical outcomes. Accordingly, the knockdown of STAU2 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 STAU2: Palladin cytoskeletal associated protein (PALLD), Heterogeneous nuclear ribonucleoprotein U (HNRNPU), SERPINE1 mRNA Binding Protein 1 (SERBP1), and DEAD-box polypeptide 3, X-Linked (DDX3X). Finally, we found that a high expression level of STAU2 not only helps PAAD evade the immune response but is also related to chemotherapy drug sensitivity, which implies that STAU2 could serve as a potential target for combinatorial therapy. These findings uncovered a novel role for STAU2 in PAAD aggression and resistance, suggesting that it probably represents a novel therapeutic and drug development target.

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression

“…Additionally, subsequent research has shown that modification of the bioenergetics of PC cells could effectively influence the functionality of TRIM29 through a collaborative effort facilitated by the recruitment of miR-2355-3p and DDX3X to the AK4 transcript [ 27 ]. Recently, a noteworthy finding has emerged, underscoring the indispensable regulatory role of STAU2 in pancreatic adenocarcinoma, and DDX3X was identified as its target gene [ 28 ]. In light of these discoveries, one hypothesis suggests that the upregulation of DDX3X is a contributing factor to the advancement and dissemination of pancreatic carcinoma.…”

Impact of NDUFAF6 on breast cancer prognosis: linking mitochondrial regulation to immune response and PD-L1 expression

“…Immune infiltration is pivotal in the tumor microenvironment and is closely related to tumor growth, metastasis, and treatment response [19]. PD-L1 is a crucial immune checkpoint, and its expression on tumor cells is associated with immune evasion and poor prognosis [20].…”