Gene Regulation by Antitumor in Pancreatic Ductal Adenocarcinoma: The Clinical Significance of Direct RACGAP1 Regulation.

Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of . Here, we aimed to investigate the functional significance of and to identify target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of in PDAC cells. Comprehensive gene expression analyses and database searches revealed 25 putative targets regulated by in PDAC cells. Among these target genes, high expression levels of , , , , , and were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: = 0.0000548; disease-free survival rate: = 0.0014). Overexpression of was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by (e.g., , , , and ) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC.