miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM

Guo,Yuyan; Sun,Wenze; Gong,Tuotuo; Chai,Yanlan; Wang,Juan; Hui,Beina; Li,Yi; Song,Liping; Gao,Ying

doi:10.3892/or.2017.5448

miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM

Authors:
- Yuyan Guo
- Wenze Sun
- Tuotuo Gong
- Yanlan Chai
- Juan Wang
- Beina Hui
- Yi Li
- Liping Song
- Ying Gao
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Affiliations: Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: February 14, 2017 https://doi.org/10.3892/or.2017.5448
Pages: 1980-1988
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing number of studies report that microRNAs play important roles in radiosensitization. miR-30a has been proved to perform many functions in the development and treatment of cancer, and it is downregulated in non-small cell lung cancer (NSCLC) tissues and cells. This study was conducted to understand if miR-30a plays a role in the radiosensitivity of NSCLC cells. Radiosensitivity was examed by colony survival assay and tumor volume changing in vitro and in vivo, respectively. Bioinformatic analysis and luciferase reporter assays were used to distinguish the candidate target of miR-30a. qRT-PCR and western blotting were carried out to detect the relative expression of mRNAs and proteins. Cell cycle and cell apoptosis were determined by flow cytometry. Our results illustrated miR-30a could increase the radiosensitivity of NSCLC, especially in A549 cell line. In vivo experiment also showed the potential radiosensitizing possibility of miR-30a. Further exploration validated that miR-30a was directly targeting activating transcription factor 1 (ATF1). In studying the ataxia-telangiectasia mutated (ATM) associated effects on cell radiosensitivity, we found that miR-30a could reduce radiation induced G2/M cell cycle arrest and may also affect radiation induced apoptosis. Together, our results demonstrated that miR-30a may modulate the radiosensitivity of NSCLC through reducing the function of ATF1 in phosphorylation of ATM and have potential therapeutic value.

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