Extracellular vesicle-encapsulated microRNA-425 promotes tumor development and serves as a biomarker for pancreatic ductal adenocarcinoma.

BACKGROUND

MicroRNAs (miRNAs) enclosed within extracellular vesicles (EVs) have emerged as crucial players in carcinogenesis and are increasingly recognized as potential cancer biomarkers. However, their significance in pancreatic ductal adenocarcinoma (PDAC) and their utility for early detection remain unclear.

METHODS

We utilized microarray analysis to identify the miRNAs highly expressed in PDAC cells compared to immortalized pancreatic ductal cells. Functional studies investigated the effect of miRNA overexpression and inhibition on PDAC cells invasion/migration and associated signaling pathways. Additionally, we examined the transfer of miRNA via EVs and their potential impact on the recipient PDAC cells. Serum samples from 30 healthy individuals, 30 patients with intraductal papillary mucinous neoplasm, and 30 PDAC were analyzed for EV miRNA expression using digital PCR.

RESULTS

MiR-425 emerged as an oncogenic miRNA upregulated in PDAC, suppressing phosphatase and tensin homolog (PTEN) while activating phosphatidylinositol 3-kinase (PI3K)/Akt and epithelial-to-mesenchymal transition (EMT) pathways. Treatment with miR-425-enriched EVs induced EMT in PDAC cells by suppressing PTEN, enhancing invasion and migration. Serum EV miR-425 levels tended to be higher in PDAC patients, particularly in Stage I/II compared to Stage III/IV, although the difference was not statistically significant. Combining EV miR-425 with CA19-9 improved diagnostic performance over CA19-9 alone, achieving a sensitivity 93%, specificity 91%, and AUC of 0.98.

CONCLUSION

Our finding suggested the role of intercellular transfer of EV miR-425 in inducing EMT via PTEN/PI3K/Akt pathway modulation, thereby promoting invasion and migration of PDAC cells. Serum EV miR-425 holds promise as a potential biomarker for early diagnosis of PDAC.