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Metformin Inhibits the Progression of Pancreatic Cancer Through Regulating miR ‐378a‐3p/ VEGFA / RGC ‐32 Axis

Year: 2024
Type: article
Abstract: 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. 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.
DOI: 10.1002/cam4.70446
Language: English
Open Access status: gold
Estimated APC paid: $4,270
OpenAlex ID: W4404827475
FWCI: 0.579
Cites: 31
Cited by: 5
Related to: 10