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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

miR-22/KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma

Authors: Yixue Gu, Hao Liu, Fangren Kong, Jiahui Ye, Xiaoting Jia, Zhijie Zhang, Nan Li, Jiang Yin, Guopei Zheng, Zhimin He

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Tongue squamous cell carcinoma (TSCC) is the most common oral cancer. Neoadjuvant systemic treatment before or after surgery for advanced TSCC is considered one of the most crucial factors in reducing mortality. However, the therapeutic benefits of chemotherapy are usually attenuated due to intrinsic and/or acquired drug resistance, and a large proportion of TSCC are resistant to chemotherapy, which may result in more aggressive tumor behavior and an even worse clinical outcome. Recently, the potential application of using miRNAs to predict therapeutic response to cancer treatment holds high promise, but miRNAs with predictive value remain to be identified and underlying mechanisms remain to be understood in TSCC.

Methods

The expression of miR-22 in tissues from patients diagnosed with TSCC was analyzed using real-time PCR. The effects of miR-22 on cell proliferation and tumorigenesis in TSCC cells were analyzed by MTS assay, and flow cytometry. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, real-time PCR and western blot were performed to validate a potential target of miR-22 in TC. The correlation between miR-22 expression and KAT6B expression, as well as the mechanisms by which miR-22 regulates PI3k-Akt-NF-kB pathway in TSCC were also addressed.

Results

We found a strong correlation between miR-22 expression and chemosensitivity to cisplatin (CDDP) in TSCC patients. Ectopic overexpression of miR-22 enhanced TSCC cells apoptosis in response to CDDP in experimental models performed in vitro and in vivo. Moreover, we found that KAT6B is a direct functional target of miR-22. Ectopic expression of KAT6B attenuated the efficiency of miR-22 in TSCC cells upon CDDP treatment. Mechanistically, miR-22 overexpression or KAT6B knockdown inhibited PI3K/Akt/NF-κB signaling in TSCC cells, possibly via downregulating the activators of PI3K/Akt/NF-κB signaling, such as S100A8, PDGF and VEGF. Furthermore, the activation of miR-22 depended on the intensity of the stresses in the presence of p53 activation.

Conclusions

Our findings define miR-22 as an intrinsic molecular switch that determines p53-dependent cellular fate through KAT6B/ PI3K-Akt/ NF-kB pathway.
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Metadata
Title
miR-22/KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma
Authors
Yixue Gu
Hao Liu
Fangren Kong
Jiahui Ye
Xiaoting Jia
Zhijie Zhang
Nan Li
Jiang Yin
Guopei Zheng
Zhimin He
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0834-z

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