Background
Pancreatic cancer (PC) is a major contributor to global cancer-related mortality. While the inhibitory effect of metformin (Met) on PC has been reported, the underlying mechanism remains elusive.
Conclusions
Met exerted inhibitory effects on PC through the miR-378a-3p/VEGFA/RGC-32 pathway. Strategies targeting the miR-378a-3p/VEGFA/RGC-32 axis represent a novel avenue for the prevention and treatment of PC.
Methods
We established BxPC-3 cell models with miR-378a-3p and VEGFA knockdown. The expression of miR-378a-3p, VEGFA, and RGC-32 in PC and normal tissues was analyzed using GEPIA, TCGA databases. Cell proliferation, invasion, migration, and apoptosis were assessed through CCK8, Transwell, wound healing, and flow cytometry.
Results
Significantly lower expression of miR-378a-3p was observed in PC tissues and cells. Knockdown of miR-378a-3p reversed the impact of Met on cell viability in PANC-1 and BxPC3. VEGFA emerged as a potential regulator in PC and a downstream target of miR-378a-3p. The interaction between VEGFA and RGC-32 played a crucial role in PC regulation. Knockdown of VEGFA substantially reversed the impact of miR-378a-3p inhibitor on tumor growth and the epithelial-mesenchymal transition (EMT) process. Moreover, knockdown of VEGFA effectively countered the influence of miR-378a-3p inhibitor on cell viability and the EMT process in BxPC3 cells. Conclusions: Met exerted inhibitory effects on PC through the miR-378a-3p/VEGFA/RGC-32 pathway. Strategies targeting the miR-378a-3p/VEGFA/RGC-32 axis represent a novel avenue for the prevention and treatment of PC.