We elucidate in this study that up-regulation of miR-574-5p in gastric cancer cells under hypoxic conditions contributed to angiogenesis. We found that miR-574-5p and HIF-1α were up-regulated in gastric cancer cells cultured under 2% O2 or in medium containing CoCl2, and in muscle tissues of mice injected with NaNO2, indicating up-regulation of miR-574-5p in vitro or in vivo in response to hypoxic conditions. We hypothesized that up-regulation of miR-574-5p could promote angiogenesis. Transfection of gastric cancer cells with miR-574-5p mimics or inhibitor resulted in increase or decrease in the expression of VEGFA. Viability, migration, invasion and tube formation of HUVECs cultured with conditioned medium from SGC/574 cells transfected with miR-574-5p inhibitor were reduced. Tube formation of HUVECs cultured with conditioned medium from SGC-7901 cells transfected with miR-574-5p mimics was increased. An in vivo study demonstrated that inhibition of miR-574-5p in the tumor xenografts of mice reduced the expression of CD31 one of the endothelial cell markers. We identified PTPN3 a tyrosine phosphatase as a target of miR-574-5p that bound to the 3'UTR of PTPN3 mRNA to inhibit the expression of PTPN3. Furthermore, the data in this study demonstrated that inhibition of PTPN3 in gastric cancer cells enhanced phosphorylation of p44/42 MAPKs and promoted angiogenesis. We conclude that miR-574-5p in gastric cancer cells promoted angiogenesis via enhancing phosphorylation of p44/42 MAPKs by miR-574-5p inhibition of PTPN3 expression.
Keywords: Angiogenesis; Gastric cancer; MAPK; PTPN3; VEGF; miR-574-5p.
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