MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3 (PTPN3).
MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3 (PTPN3).
复制标题
DOI：
10.1016/j.gene.2020.144383
复制
发表时间：
2020-01
期刊：
影响因子：
3.5
通讯作者：
Shu Zhang;Renwen Zhang;R. Xu;Jiaqi Shang;Haitao He;Q. Yang
中科院分区：
文献类型：
--
作者：
Shu Zhang;Renwen Zhang;R. Xu;Jiaqi Shang;Haitao He;Q. Yang
我们在这项研究中阐明，在缺氧条件下，胃癌细胞中miR-574- 5 p的上调有助于血管生成。我们发现miR-574- 5 p和HIF-1α在2%O2或含CoCl 2的培养基中培养的胃癌细胞以及注射NaNO 2的小鼠肌肉组织中上调，表明miR-574- 5 p在体外或体内响应于低氧条件而上调。我们推测上调miR-574- 5 p可以促进血管生成。用miR-574- 5 p模拟物或抑制剂转染胃癌细胞导致VEGFA表达的增加或减少。用来自转染miR-574- 5 p抑制剂的SGC/574细胞的条件培养基培养的HUVECs的活力、迁移、侵袭和管形成降低。用来自用miR-574- 5 p模拟物转染的SGC-7901细胞的条件培养基培养的HUVEC的管形成增加。一项体内研究表明，抑制小鼠肿瘤异种移植物中的miR-574- 5 p可降低内皮细胞标志物之一CD 31的表达。我们发现PTPN 3是一种酪氨酸磷酸酶，是miR-574- 5 p的靶点，它与PTPN 3 mRNA的3′UTR结合，抑制PTPN 3的表达。此外，本研究中的数据表明，在胃癌细胞中抑制PTPN 3增强了p44/42 MAPK的磷酸化并促进血管生成。我们得出的结论是，胃癌细胞中的miR-574 - 5 p通过抑制PTPN 3表达来增强p44/42 MAPKs的磷酸化，从而促进血管生成。
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% O2or 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.