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

: 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.