State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
Mol Biol Cell. 2012 Apr;23(8):1423-34. doi: 10.1091/mbc.E11-09-0777. Epub 2012 Feb 22.
Dysexpression of microRNAs has been found in many tumors, including lung cancer. The hedgehog (Hh) signaling pathway plays an important role during normal development, and the abnormal regulation of its members has also been related to many tumors. However, little is known about the relationship between microRNA and the Hh pathway. In this paper, we report microRNA-212 (miR-212) playing a role in non-small cell lung cancer (NSCLC) and targeting PTCH1, a receptor of the Hh pathway. We found that miR-212 was up-regulated when cells were treated with 4ß-12-O-tetradecanoylphorbol-13-acetate (TPA). We ectopically expressed miR-212 in NSCLC cell lines to examine the influence of miR-212 overexpression. The results showed that overexpression of miR-212 in NSCLC cells promoted cell cycle progression and cell proliferation, migration, and invasion. The promoting effects of miR-212 on cell proliferation, migration, and invasion were partially reversed by the miR-212 inhibitor anti-miR-212. These results suggested that miR-212 might have tumor-promoting properties. Potential targets of miR-212 were predicted, and we showed tumor suppressor PTCH1 was a functional target of miR-212. PTCH1 may be responsible for the effect of miR-212 on cell proliferation. Altogether, our results indicated that miR-212 was involved in tumorigenesis, and the oncogenic activity of miR-212 in NSCLC cells was due, in part, to suppression of PTCH1.
微 RNA 的表达失调已在许多肿瘤中被发现，包括肺癌。Hedgehog（Hh）信号通路在正常发育过程中发挥重要作用，其成员的异常调节也与许多肿瘤有关。然而，微 RNA 与 Hh 通路之间的关系知之甚少。在本文中，我们报告了 microRNA-212（miR-212）在非小细胞肺癌（NSCLC）中发挥作用，并靶向 Hh 通路的受体 PTCH1。我们发现细胞用 4ß-12-O-十四烷酰佛波醇-13-醋酸酯（TPA）处理时 miR-212 上调。我们在 NSCLC 细胞系中外源性表达 miR-212 以检测 miR-212 过表达的影响。结果表明，NSCLC 细胞中 miR-212 的过表达促进细胞周期进程和细胞增殖、迁移和侵袭。miR-212 抑制剂 anti-miR-212 部分逆转了 miR-212 对细胞增殖、迁移和侵袭的促进作用。这些结果表明 miR-212 可能具有促进肿瘤的特性。预测了 miR-212 的潜在靶标，我们表明肿瘤抑制因子 PTCH1 是 miR-212 的功能靶标。PTCH1 可能是 miR-212 对细胞增殖影响的原因。总之，我们的结果表明 miR-212 参与了肿瘤发生，miR-212 在 NSCLC 细胞中的致癌活性部分归因于对 PTCH1 的抑制。
