Background

MicroRNA-34a (miR-34a) has been reported to inhibit TGF-β (transforming growth factor-β)-induced epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma (NPC). However, the underlying mechanism remain unclear. Using the bioinformatics, we found that the AXL receptor tyrosine kinase (AXL) is a predicted target of miR-34a.

Objective

we aimed to reveal the relationship between miR-34a and AXL, and investigate the effect and mechanism of miR-34a in NPC progression.

Methods

The expression patterns of miR-34a and AXL in 30 paired NPC tissues and the adjacent tissues were examined by quantitative real time PCR (qRT-PCR). The target relationship between miR-34a and AXL was evaluated by the luciferase gene reporter assay. Cell migration and invasion were assessed by wound healing and transwell chamber assays, respectively.

Results

miR-34a level was dramatically decreased in the NPC tissues compared to the adjacent tissues, while AXL expression was increased. Overexpression of miR-34a significantly reduced the luciferase activity of the luciferase vector of AXL (pGL3-AXL-WT), whereas this effect was abrogated when binding sites between miR-34a and AXL were mutated. In addition, ectopic expression of miR-34a dramatically inhibited Sune-1 cell migration and invasion abilities, decreased the levels of N-cadherin and Vimentin and increased E-cadherin and γ-catenin expressions, as well as induced significant reductions in the expressions of p-AKT and Snail. However, these effects were attenuated when the cells were treated with recombinant human AXL protein.

Conclusions

Our results demonstrate that miR-34a/AXL can inhibit NPC cell migration, invasion and EMT through inhibition of AKT/Snail signaling.

中文翻译：

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MicroRNA-34a通过靶向鼻咽癌中的AXL / PI3K / AKT / Snail信号传导抑制细胞侵袭和上皮-间质转化。

背景

MicroRNA-34a（miR-34a）在鼻咽癌（NPC）中抑制TGF-β（转化生长因子-β）诱导的上皮-间质转化（EMT）。但是，其潜在机制仍不清楚。使用生物信息学，我们发现AXL受体酪氨酸激酶（AXL）是miR-34a的预期靶标。

目的

我们旨在揭示miR-34a与AXL之间的关系，并探讨miR-34a在NPC进程中的作用和机制。

方法

通过定量实时荧光定量PCR（qRT-PCR）检测miR-34a和AXL在30对配对的NPC组织和邻近组织中的表达模式。miR-34a和AXL之间的靶标关系通过萤光素酶基因报告基因分析进行了评估。细胞迁移和侵袭分别通过伤口愈合和transwell室测定法进行评估。

结果

与邻近组织相比，NPC组织中的miR-34a水平显着降低，而AXL表达增加。miR-34a的过表达显着降低了AXL萤光素酶载体（pGL3-AXL-WT）的萤光素酶活性，而当miR-34a和AXL之间的结合位点发生突变时，这种作用就消失了。此外，miR-34a的异位表达显着抑制了Sune-1细胞的迁移和侵袭能力，降低了N-钙粘蛋白和波形蛋白的水平，并增加了E-钙粘蛋白和γ-连环蛋白的表达，并诱导了其表达的显着降低。 p-AKT和蜗牛。但是，用重组人AXL蛋白处理细胞后，这些作用减弱了。

结论

我们的结果表明，miR-34a / AXL可通过抑制AKT / Snail信号传导来抑制NPC细胞的迁移，侵袭和EMT。