Department of Pathophysiology, Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Pathophysiology, Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Rep. 2018 Jun;39(6):2613-2623. doi: 10.3892/or.2018.6352. Epub 2018 Apr 4.
IL‑13 is a proinflammatory cytokine associated with multiple pathological conditions and the promotion of metastasis in lung cancer. Previous studies have demonstrated that IL‑13 and YY1 are associated with PI3K/AKT signaling. In addition, miR‑29a has been found to play a critical role in cell invasion in lung cancer. However, the molecular mechanism of miR‑29a underlying its involvement in IL‑13‑induced lung cancer cell invasion remains largely unknown. In the present study, we aimed to investigate the role of miR‑29a in cell invasion mediated by IL‑13 in lung cancer. By using MTT and wound‑scratch assays, we assessed cell proliferation and migration induced by IL‑13, and identified activation of the PI3K/AKT/YY1 pathway. Inhibition of PI3K/AKT by LY294002 downregulated IL‑13‑induced YY1 expression. Furthermore, we found that miR‑29a directly targets YY1 and suppressed its expression in lung cancer. By using MTT, flow cytometry and Transwell assays, overexpression of miR‑29a restricted both YY1 and N‑cadherin expression, and inhibited IL‑13‑induced invasion of lung cancer A549 cells. Taken together, these findings demonstrate that PI3K/AKT/YY1 is involved in the regulation of lung cancer cell behavior induced by IL‑13, and miR‑29a represents a promising therapeutic target.
白细胞介素 13(IL-13)是一种促炎细胞因子,与多种病理状况和肺癌的转移促进有关。先前的研究表明,IL-13 和 YY1 与 PI3K/AKT 信号通路有关。此外,miR-29a 已被发现在肺癌细胞侵袭中发挥关键作用。然而,miR-29a 参与 IL-13 诱导的肺癌细胞侵袭的分子机制在很大程度上仍不清楚。在本研究中,我们旨在研究 miR-29a 在 IL-13 诱导的肺癌细胞侵袭中的作用。通过 MTT 和划痕实验,我们评估了 IL-13 诱导的细胞增殖和迁移,并确定了 PI3K/AKT/YY1 通路的激活。LY294002 抑制 PI3K/AKT 下调了 IL-13 诱导的 YY1 表达。此外,我们发现 miR-29a 直接靶向 YY1 并抑制其在肺癌中的表达。通过 MTT、流式细胞术和 Transwell 实验,miR-29a 的过表达限制了 YY1 和 N-钙黏蛋白的表达,并抑制了 IL-13 诱导的肺癌 A549 细胞侵袭。总之,这些发现表明 PI3K/AKT/YY1 参与了 IL-13 诱导的肺癌细胞行为的调节,miR-29a 代表了一种有前途的治疗靶点。