Fig 1: LRRN1 exerts its biological functions through the Notch signaling pathway(A and B) GEPIA and TIMER databases were used to investigate the correlation between LRRN1 and HIF-1a, Notch1, as well as downstream Hes1 at the transcriptional levels (Spearman correlation). (C) IHC staining of PDAC tissues in different regions for LRRN1, including the junction of tumor tissue and adjacent normal tissue (normoxia zone) and the central area of fibrotic encapsulation (hypoxia zone). The red arrow points to the blood vessel. White bar, 100 µm; black bar, 20 µm. (D) IF staining of LRRN1 (red) and HIF-1a (green) in sh-LRRN1 group and control group by using xenograft murine subcutaneous bearing model (AsPC-1). White bar, 20 µm. (E) LRRN1 knockdown impaired the expression of HIF-1a/Notch pathway-related protein, including HIF-1a, Notch1, NICD, and Hes1. (F) The recombinant JAG1 stimulated the activation of Notch signaling, but this effect could be strongly dampened by the shRNA-mediated LRRN1 knockdown. (G) Schematic representation of LRRN1 promoting PDAC progression through the HIF-1a/Notch signaling pathway. *p < 0.05, **p < 0.01, ***p < 0.001.