1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China.
Cell Transplant. 2019 Mar;28(3):306-317. doi: 10.1177/0963689719825573. Epub 2019 Jan 30.
MicroRNA plays a pivotal role in various human cancers, especially in human gastric cancer. In the present study, we evaluated the effect of microRNA-21 (miR-21) on the gastric cancer cell proliferation, migration, apoptosis and the related signaling cascades. Here, we showed that down-regulation of miR-21 markedly reduced gastric cancer cell proliferation (AGS and NCI-N87 cells) in a time dependent manner. Moreover, our findings revealed that silencing miR-21 dramatically blocked gastric cancer cell migration and movement, which might be related to down-regulation of vimentin expression. We also found that down-regulation of miR-21 promoted cell apoptosis and repressed cell cycle progression. Further investigation showed that down-regulation of miR-21 significantly increased phosphatase and tensin homolog (PTEN) protein expression level, but not transcription level (mRNA level), which in turn decreased Akt phosphorylation at Thr308 and Ser473. Collectively, our results uncover that miR-21 targets PTEN/Akt signaling pathway and regulates cell proliferation, migration and apoptosis in human gastric cancer cells. Our findings may provide a therapeutic target for treatment of human gastric cancer.
微小 RNA 在各种人类癌症中发挥着关键作用，尤其是在人类胃癌中。在本研究中，我们评估了微小 RNA-21（miR-21）对胃癌细胞增殖、迁移、凋亡及相关信号级联的影响。研究结果表明，miR-21 的下调显著地呈时间依赖性降低胃癌细胞增殖（AGS 和 NCI-N87 细胞）。此外，我们的研究结果揭示，沉默 miR-21 显著抑制胃癌细胞迁移和运动，这可能与波形蛋白表达下调有关。我们还发现，miR-21 的下调促进细胞凋亡并抑制细胞周期进程。进一步的研究表明，miR-21 的下调显著增加磷酸酶和张力蛋白同源物（PTEN）蛋白表达水平，但不影响转录水平（mRNA 水平），从而降低 Akt 在 Thr308 和 Ser473 处的磷酸化。综上所述，我们的研究结果揭示了 miR-21 靶向 PTEN/Akt 信号通路，并调节人类胃癌细胞的增殖、迁移和凋亡。我们的研究结果可能为人类胃癌的治疗提供一个治疗靶点。
