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KMID : 0381120200420080971
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Genes and Genomics
2020 Volume.42 No. 8 p.971 ~ p.978
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MicroRNA-34a inhibits cell invasion and epithelial-mesenchymal transition via targeting AXL/PI3K/AKT/Snail signaling in nasopharyngeal carcinoma
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Jiang Chengyi
Cheng Zhongqiang
Jiang Tao
Xu Yajia
Wang Bin
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Abstract
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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.
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KEYWORD
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miR-34a, AXL, AKT/Snail signaling, Migration, Invasion
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