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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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Abstract

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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Acknowledgements

Not applicable.

Funding

This work was supported by Anhui Provincial Key Project of Natural Science Research in Institutions of Higher Learning in 2018 (Grant No. KJ2018A0996) and 2017 Bengbu Medical College General Program (Grant No. BYKY1772).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu City, 233004, Anhui Province, China

    Chengyi Jiang, Zhongqiang Cheng, Tao Jiang, Yajia Xu & Bin Wang

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  1. Chengyi Jiang
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  2. Zhongqiang Cheng
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  3. Tao Jiang
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  4. Yajia Xu
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  5. Bin Wang
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Contributions

CYJ and ZQC conceived and designed the experiments,TJ and YJX analyzed and interpreted the results of the experiments, BW performed the experiments.

Corresponding author

Correspondence to Chengyi Jiang.

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Conflict of Interest

Chengyi Jiang, Zhongqiang Cheng, Tao Jiang, Yajia Xu and Bin Wang state that there are no conflicts of interest to disclose.

Ethics approval and consent to participate

All procedures in the current study involving human samples were performed in accordance with the Helsinki declaration and approved by the Ethic Committee of The First Affiliated Hospital of Bengbu Medical College. The informed consent has been obtained from each participant.

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Supplementary Fig. 1

Evaluation of the expression of known targets of miR-34a. QRT-PCR was performed to detect the mRNA levels of (A) SIRT1, (B) CD44, (C) c-MET, (D) CDK6 and (E) cyclin D1 after Sune-1 cells were transfected with NC mimic or miR-34a mimic. Three independent experiments were carried out. (n = 03, *P<0.05, **P<0.01). 1 (TIF 272.0 kb)

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Jiang, C., Cheng, Z., Jiang, T. et al. MicroRNA-34a inhibits cell invasion and epithelial-mesenchymal transition via targeting AXL/PI3K/AKT/Snail signaling in nasopharyngeal carcinoma. Genes Genom 42, 971–978 (2020). https://doi.org/10.1007/s13258-020-00963-3

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