Department of Respiratory Medicine, The 454 Hospital of PLA, Nanjing, Jiangsu 210002, P.R. China.
Int J Mol Med. 2014 Jul;34(1):307-12. doi: 10.3892/ijmm.2014.1764. Epub 2014 Apr 30.
Toll-like receptor 9 (TLR9) has been shown to have a significant role in cancer. MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are involved in the development and progression of human cancers. The present study was undertaken to determine the roles of TLR9 on lung cancer and whether miR-26a is involved in TLR9‑mediated lung cancer growth and migration. The lung cancer models were elicited by injecting human lung cancer cells into the left ventricle. The expression of TLR9 and miR-26a in lung cancer tissues obtained from lung cancer patients was increased. TLR9 ligand CpG-oligodeoxynucleotides (CpG-ODN) caused an increase in the mean tumor weight and the size of tumor mass in nude mice, and the proliferation and migration of H460 human lung cancer cells. CpG-ODN also induced an increase in the expression of miR-26a in H460 cells. The overexpression of miR-26a increased the weight and size of the tumor mass in the nude mice, and the proliferation and migration of H460 cells. Expression of phosphoinositide 3 kinase (PI3K) and phosphorylation of protein kinase B (Akt) was increased after miR-26a overexpression in the H460 cells. PI3K inhibitor wortmannin (WM) or Akt inhibitor triciribine hydrate (TCN) eliminated the increase in the proliferation and migration induced by the overexpression of miR-26a in H460 cells. These results suggested that miR-26a is involved in the TLR9‑mediated growth and migration of lung cancer through the PI3K-Akt signaling pathway.
Toll 样受体 9（TLR9）在癌症中具有重要作用。微小 RNA（miRNA）是一组调节多个靶 mRNA 翻译的小非编码 RNA，参与人类癌症的发生和发展。本研究旨在确定 TLR9 在肺癌中的作用，以及 miR-26a 是否参与 TLR9 介导的肺癌生长和迁移。通过将人肺癌细胞注入左心室来建立肺癌模型。从肺癌患者的肺癌组织中检测到 TLR9 和 miR-26a 的表达增加。TLR9 配体 CpG-寡脱氧核苷酸（CpG-ODN）导致裸鼠中肿瘤平均重量和肿瘤块大小增加，以及 H460 人肺癌细胞的增殖和迁移增加。CpG-ODN 还诱导 H460 细胞中 miR-26a 的表达增加。miR-26a 的过表达增加了裸鼠肿瘤块的重量和大小，以及 H460 细胞的增殖和迁移。在 H460 细胞中转染 miR-26a 后，磷酸肌醇 3 激酶（PI3K）的表达和蛋白激酶 B（Akt）的磷酸化增加。PI3K 抑制剂渥曼青霉素（WM）或 Akt 抑制剂三尖杉酯碱水合物（TCN）消除了 miR-26a 过表达诱导的 H460 细胞增殖和迁移的增加。这些结果表明，miR-26a 通过 PI3K-Akt 信号通路参与 TLR9 介导的肺癌生长和迁移。
