miR-193a-5p靶向VASP干扰PI3K/AKT信号通路抑制胃癌细胞增殖和诱导细胞凋亡的机制研究

Mechanism of miR-193a-5p Interfering with PI3K/AKT Signaling Pathway by Targeting VASP to Inhibit Cell Proliferation and Induce Cell Apoptosis of Gastric Cancer

目的分析miR-193a-5p影响胃癌细胞增殖和凋亡的具体作用机制。方法采用RT-qPCR和Western blot法检测60例胃癌组织、癌旁组织和细胞中miR-193a-5p和VASP蛋白的表达;采用CCK-8法和流式细胞术检测miR-193a-5p和VASP对胃癌细胞BGC-823和SGC7901增殖和凋亡的影响;双荧光素酶报告基因实验检测VASP与miR-193a-5p间的靶向作用关系;Western blot法检测miR-193a-5p对PI3K/AKT信号通路的影响。结果在胃癌组织和胃癌细胞BGC-823和SGC7901中,miR-193a-5p表达显著降低,而VASP表达则显著上调;miR-193a-5p过表达或敲低VASP可抑制胃癌细胞的增殖并诱导细胞凋亡,与沉默miR-193a-5p或VASP过表达结果相反;双荧光素酶报告基因实验证实VASP是miR-193a-5p的靶基因,且miR-193a-5p可调控VASP表达;miR-193a-5p过表达可干扰PI3K/AKT信号通路,而外源回补VASP则可部分逆转miR-193a-5p对PI3K/AKT信号通路活性的抑制作用。结论miR-193a-5p通过靶向VASP干扰PI3K/AKT信号通路,进而抑制胃癌细胞增殖和诱导细胞凋亡。

Objective To analyze the specific mechanism of mir-193a-5p influencing proliferation and apoptosis of gastric cancer cells.Methods Real time-quantitative polymerase chain reaction(RT-qPCR)and Western blot methods were used to detect expressions of miR-193a-5p and VASP proteins in gastric cancer tissues,adjacent tissues and cells of 60 patients.CCK-8 method and flow cytometry were used to detect effects of miR-193a-5p and VASP on proliferation and apoptosis of BGC-823 and SGC7901 in gastric cancer cells.Dual luciferase reporter gene assay was used to detect the targeting relationship between VASP and miR-193a-5p.Western blot was employed to detect effect of miR-193a-5p on PI3K/AKT signaling pathway.Results In gastric cancer tissues and BGC-823 and SGC7901 in gastric cancer cells,expressions of miR-193a-5p were significantly decreased,while VASP expressions were significantly increased;overexpression or knockdown of miR-193a-5p could inhibit proliferation of gastric cancer cells and induce apoptosis,which was contrary to results of silencing miR-193a-5p or VASP overexpression.Dual luciferase reporter gene assay confirmed that VASP was the target gene of miR-193a-5p,and miR-193a-5p could regulate VASP expression.Overexpression of miR-193a-5p could interfere with PI3K/AKT signaling pathway,while exogenous supplementation of VASP could partially reverse the inhibitory effect of miR-193a-5p on PI3K/AKT signaling pathway activation.Conclusion The miR-193a-5p may inhibit proliferation and induce apoptosis of gastric cancer cells by targeting VASP and interfering with PI3K/AKT signaling pathway.