<p>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</p>

Abstract

BackgroundAbnormal 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 methodsThe 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.ResultsMiR-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.ConclusionUpregulated 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.

<p>Long Noncoding RNA PVT1 Promotes Prostate Cancer Metastasis by Increasing NOP2 Expression via Targeting Tumor Suppressor MicroRNAs</p>

“…20 In addition, upregulating the expression of 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. 21 Furthermore, it has been shown that miR-143-3p targeting of ITGA6 suppresses tumor growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma. 22 In this study, we also found that miR-15b-5p, miR-27a-3p, miR-143-3p, and miR-627-5p were closely related with PVT1 and NOP2.…”

Inverse Correlation of miR-27a-3p&nbsp;and CDH5&nbsp;Expression Serves as a Diagnostic Biomarker of Proliferation and Metastasis of Clear Cell Renal Carcinoma

“…[25,[32][33][34] Mir-27a-3p has been identi ed to promote tumor invasion and metastasis in gastric, colon, pancreatic, and nasopharyngeal cancers. [35][36][37][38] On the other hand, a tumor suppressor role has also been shown for miR-27a-3p in some cancers. For instance, it inhibits the proliferation of non-small cell lung cancer cells by targeting HOXB8.…”

The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer

“…Several studies demonstrated that miR-27-3p promotes and suppresses the metastasis of pancreatic cancer and hepatocellular carcinoma, respectively [ 80 , 81 ], suggesting the dual role of this miRNA in a cellular context-dependent manner. Another study showed that the anchorage-independent growth of osteosarcoma cells is accelerated by miR-27-3p, whose expression is upregulated in cancer cells in comparison with normal osteocyte cells [ 31 ].…”