Upregulated miR-27a-3p indicates a poor prognosis in pancreatic carcinoma patients and promotes the angiogenesis and migration by epigenetic silencing of GATA6 and activating VEGFA/VEGFR2 signaling pathway

Abstract

Background: Abnormal miR-27a-3p expression has been frequently reported in several types of human cancer and contributes to tumor progression. However, the role and potential molecular mechanism of miR-27a-3p in the progression of pancreatic carcinoma have not been clarified. Materials and methods: The expression of miR-27a-3p and GATA binding protein 6 (GATA6) in pancreatic carcinoma tissues and cell lines was evaluated by quantitative real-time PCR and Western blotting analysis. The relationship between clinical pathologic features and miR-27a-3p expression was analyzed with Chi-square test. The regulatory mechanism of miR-27a-3p on GATA6 was confirmed by luciferase reporter assay and bioinformatics analysis. The effects of miR-27a-3p by targeting GATA6 on cell angiogenesis and migration were assessed by capillary tube formation and wound healing assays. Results: MiR-27a-3p expression was significantly upregulated in pancreatic carcinoma tissues and cell lines. Highly expressed miR-27a-3p was closely related to more lymph node metastasis, present peritoneal metastasis, and poor prognosis in patients with pancreatic carcinoma. MiR-27a-3p promoted migration and angiogenesis of pancreatic carcinoma cells by activating vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor 2 (VEGFR2) expression. A significantly negative correlation between GATA6 mRNA and miR-27a-3 expression was found in pancreatic carcinoma samples. Modulation of miR-27a-3p could alter GATA6 expression in pancreatic carcinoma cells. GATA6 was identified as a functional target gene of miR-27a-3p, and GATA6 knockdown partially reversed the effects of miR-27a-3p siliencing on the migration and angiogenesis of pancreatic carcinoma cells by regulation of VEGFA/VEGFR2 pathway. Conclusion: Upregulated miR-27a-3p indicates a poor prognosis in pancreatic carcinoma patients and promotes the angiogenesis and migration by epigenetic silencing of GATA6 and activating VEGFA/VEGFR2 signaling pathway, and indicating miR-27a-3p may be a promising therapeutic target for pancreatic carcinoma treatment.