IL-6通过调控miR-152/PIK3R3通路促进胃癌细胞的增殖和上皮-间质转化

目的：探索白细胞介素(interleukin，IL)-6在胃癌中的作用及相关的分子机制。方法：50 ng/mL IL-6刺激 胃癌细胞MGC-803后，利用MTT法检测细胞增殖、划痕实验检测细胞迁移的变化，RT-qPCR实验检测E-钙黏蛋白 (E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(vimentin)、锌指转录因子Snail1和miR-152在mRNA水平的表达， Western印迹检测E-cadherin，N-cadherin，vimentin，Snail1在蛋白水平的表达；IL-6与miR-152模拟物(miR-152 mimics)单 独处理或者共同处理MGC-803细胞后，RT-qPCR检测PIK3R3在mRNA水平的表达，Western印迹检测PIK3R3、蛋白激 酶B(Akt)和磷酸化-Akt(p-Akt)在蛋白水平的表达。结果：外源性IL-6明显促进MGC-803细胞的增殖与迁移(P<0.05)，降 低E-cadherin蛋白和mRNA和miR-152 mRNA的表达(P<0.01)，增加N-cadherin，vimentin，Snail1，PIK3R3蛋白和mRNA及 p-Akt蛋白的表达(P<0.05)。转染miR-152 mimics后明显降低了PIK3R3和p-Akt蛋白水平的表达(P<0.01)。同时，过表达miR-152 能够降低IL-6诱导的PIK3R3及p-Akt的表达水平(P<0.01)。各组中Akt的表达均无明显变化(P>0.05)。结论：IL-6可能是通过 下调miR-152表达，诱导PIK3R3表达，激活PI3K/Akt信号通路，从而促进胃癌细胞的增殖、迁移和上皮-间质转化。

IL-6 promotes gastric cancer cell proliferation and EMT through regulating miR-152/PIK3R3 pathway

Objective: To explore the role of interleukin (IL)-6 in gastric cancer cells and the mechanisms. Methods: Gastric cancer cells MGC-803 were treated with 50 ng/mL of recombinant IL-6 protein, and then cell viability and cell migration were detected by MTT assay and wound-healing assay, respectively. The mRNA and protein expressions of E-cadherin, N-cadherin, vimentin, Snail1 and miR-152 were analyzed by RT-qPCR and Western blot, respectively. Moreover, MGC-803 cells were simultaneously or separately treated with IL-6 and transfected with miR-152 mimics, and then the mRNA expression of PIK3R3 and the protein levels of PIK3R3, Akt and p-Akt were determined. Results: IL-6 stimulation significantly promoted cell proliferation and migration, reduced the expression of E-cadherin and miR-152, and increased the expression of N-cadherin, vimentin, Snail1, PIK3R3 and p-Akt (All P<0.05). The protein levels of PIK3R3 and p-Akt were significantly decreased after transfecting miR-152 mimics into MGC-803 cells (P<0.01). miR-152 overexpression down-regulated IL-6-induced the protein expression of PIK3R3 and p-Akt (P<0.01). The levels of Akt in each group were not changed. Conclusion: IL-6 up-regulates PIK3R3 expression and activates PI3K/Akt signaling pathway through down-regulating miR-152 expression, which consequently promotes gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition.