miR-511 induces the apoptosis of radioresistant lung adenocarcinoma cells by triggering BAX

Zhang,Han-Han; Pang,Min; Dong,Wei; Xin,Jia-Xuan; Li,You-Jie; Zhang,Zi-Cheng; Yu,Liang; Wang,Ping-Yu; Li,Bao-Sheng; Xie,Shu-Yang

doi:10.3892/or.2014.2973

miR-511 induces the apoptosis of radioresistant lung adenocarcinoma cells by triggering BAX

Authors:
- Han-Han Zhang
- Min Pang
- Wei Dong
- Jia-Xuan Xin
- You-Jie Li
- Zi-Cheng Zhang
- Liang Yu
- Ping-Yu Wang
- Bao-Sheng Li
- Shu-Yang Xie
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Affiliations: Key Laboratory of Tumour Molecular Biology, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin 300060, P.R. China, Department of Radiotherapy, The Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264000, P.R. China, Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan 250117, P.R. China
Published online on: January 9, 2014 https://doi.org/10.3892/or.2014.2973
Pages: 1473-1479

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Abstract

Radioresistance is one of the main reasons for the failure of radiotherapy in lung cancer. The present study was conducted to identify the role of miR-511 in suppressing the growth of radioresistant lung adenocarcinoma cells. First, a radioresistant A549/R cell line was generated after prolonged exposure to X-rays for 68 Gy (2 Gy/day, 5 days/week) and the radioresistance was confirmed by wound healing assay. Next, oncogenic TRIB2 was found to be upregulated in the radioresistant A549/R cells when compared to that of the control A549 cells as determined by western blot analysis. As the upstream miRNA, quantitative PCR showed that miR-511 expression was decreased in the radioresistant A549/R cells. Overexpression of miR-511 in miR-511-transfected A549/R cells inhibited cell growth and increased the number of apoptotic cells when compared with the control treatment. Flow cytometric analysis further demonstrated that the growth suppressive effect of miR-511 on A549/R cells was mediated by regulation of the cell cycle, most likely due to a block in the G1-S transition. Finally, our results showed that the expression of BAX was lower in the radioresistant A549/R cells when compared with that in the control A549 cells. After downregulation of TRIB2 by miR-511 treatment, BAX expression was obviously increased in the miR-511-transfected apoptotic A549/R cells when compared to that in the NC-treated or control cultures. In summary, our results revealed that miR-511 regulates the growth of radioresistant A549/R cells by increasing BAX expression through TRIB2, which suggests that miR-511 may be a potential therapeutic molecule for the treatment of radioresistant lung adenocarcinoma.

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