Exosomal SOX21-AS1 Regulates EREG by Sponging miR-451a and Promotes the Malignancy of Pancreatic Ductal Adenocarcinoma.

ABSTRACT

The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have increased. Exosomes, as a regulatory mode of intercellular communication, contain lncRNAs. SOX21-AS1 has been studied in other cancers, and its expression is elevated in PDAC, but its role in PDAC remains unclear. First, we analyzed the expression of lncRNAs in PDAC tissues and nontumor tissues through the TCGA database. Next, the results of the RT-qPCR experiment confirmed the prediction that the expression of SOX21-AS1 was elevated in PDAC tissues. In vivo and in vitro cell function assays confirmed that the degree of malignancy of PDAC was proportional to the expression of SOX21-AS1. In addition, through exosome isolation and uptake experiments, we first found that PDAC could secrete exosomal SOX21-AS1 and play an angiogenic role in HUVECs. Subsequently, the relationship between SOX21-AS1, miR-451a and epiregulin (EREG) was verified through database prediction and analysis and RIP assays. Finally, functional recovery assays in vivo and in vitro verified that SOX21-AS1 regulates the expression of EREG through combination with miR-451a and thus promotes the malignancy of PDAC. SOX21-AS1 was upregulated in PDAC. The upregulation of SOX21-AS1 can stimulate the proliferation, migration, invasion, stemness and epithelial-mesenchymal transition (EMT) progression of PDAC cells. Furthermore, PDAC cells secrete exosomal SOX21-AS1, which is absorbed by HUVECs and promotes angiogenesis. Our study first identified that SOX21-AS1 promotes the malignancy of PDAC through the SOX21-AS1/miR-451a/EREG axis, and also that exosomal SOX21-AS1 promotes angiogenesis in PDAC.