OncoTargets and Therapy (Dec 2019)
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
Xuefeng Rao,1 Lihui Wan,2 Zhigang Jie,3 Xiaoliang Zhu,1 Junxiang Yin,1 Hong Cao1 1Department of General Surgery, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Gastroenterology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaCorrespondence: Lihui WanDepartment of Gastroenterology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, No. 92, Aiguo Road, Donghu District, Nanchang 330006, People’s Republic of ChinaTel +86-791-86896220Email [email protected]: 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.Keywords: miR-27a-3p, pancreatic carcinoma, GATA6, migration, VEGFA/VEGFR2
