MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1.
MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1.
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MicroRNA-212 在非小细胞肺癌细胞中显示出促肿瘤特性，并靶向刺猬通路受体 PTCH1
DOI：
10.1091/mbc.e11-09-0777
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发表时间：
2012-04
影响因子：
3.3
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Li Y;Zhang D;Chen C;Ruan Z;Li Y;Huang Y
在非小细胞肺癌细胞中，过表达microRNA-212促进细胞周期进程和细胞增殖、迁移和侵袭。PTCH1是hedgehog通路的受体，是miR-212的功能靶点。miR-212在细胞增殖中的作用可能通过PTCH1介导。在包括肺癌在内的许多肿瘤中都发现了microrna的表达异常。hedgehog （Hh）信号通路在正常发育过程中起着重要作用，其成员的异常调控也与许多肿瘤有关。然而，人们对microRNA与Hh通路之间的关系知之甚少。在本文中，我们报道了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，当细胞被4ß-12- o - tetradecanoylphorol -13-acetate （TPA）处理时，miR-212上调。我们在NSCLC细胞系中异位表达miR-212以检测miR-212过表达的影响。结果显示，在NSCLC细胞中过表达miR-212可促进细胞周期进程和细胞增殖、迁移和侵袭。miR-212对细胞增殖、迁移和侵袭的促进作用被miR-212抑制剂anti-miR-212部分逆转。这些结果表明miR-212可能具有促进肿瘤的特性。预测了miR-212的潜在靶点，我们发现肿瘤抑制因子PTCH1是miR-212的功能靶点。PTCH1可能与miR-212对细胞增殖的影响有关。总之，我们的研究结果表明，miR-212参与了肿瘤的发生，miR-212在NSCLC细胞中的致癌活性部分是由于PTCH1的抑制。
Overexpression of microRNA-212 promoted cell cycle progression and cell proliferation, migration, and invasion in non–small cell lung cancer cells. PTCH1, a receptor of hedgehog pathway, is a functional target of miR-212. The role of miR-212 in cell proliferation may be mediated by PTCH1. 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.