circPLEKHM1 promotes tumor growth and metastasis through enhancing FXR1-mediated protein translation in PDAC

Circular RNAs (circRNAs) are increasingly recognized as pivotal regulators of cancer development, yet their functional roles in pancreatic ductal adenocarcinoma (PDAC) remain largely elusive. Here, we identify circPLEKHM1 as a significantly upregulated circRNA in PDAC tumors, with elevated expression strongly correlated with poor patient prognosis. Functional in vitro and in vivo analyses establish an oncogenic role for circPLEKHM1, demonstrating that its overexpression promotes tumor growth and metastasis, while its knockdown exerts suppressive effects. Mechanistically, circPLEKHM1 directly interacts with the RNA-binding protein FXR1, thereby preventing TRIM56-mediated proteasomal degradation of FXR1 and enhancing global protein synthesis. Notably, serum levels of circPLEKHM1 are significantly elevated in PDAC patients compared to healthy controls and individuals with other pancreatic conditions. Importantly, combining circPLEKHM1 with CA19-9 substantially improves diagnostic accuracy of PDAC detection. Collectively, these findings delineate circPLEKHM1 as a critical driver of PDAC progression and highlight its promise as robust liquid biopsy biomarker for PDAC diagnosis and prognosis assessment.