miR-21 modulates the effect of EZH2 on the biological behavior of human lung cancer stem cells in vitro

// Hui Xia 1, 2, 3 , Wen Zhang 1 , Baoshi Zhang 1 , Yingnan Zhao 1 , Yunlong Zhao 1 , Shaojun Li 1 and Yang Liu 2 1 Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing, China 2 Department of Thoracic Surgery, PLA General Hospital, Beijing, China 3 Medical School of PLA, Beijing, China Correspondence to: Hui Xia, email: 304xiahui@sina.com Yang Liu, email: China liuyangplats@126.com Keywords: miR-21, EZH2, lung cancer stem cells, radiotherapy, chemotherapy Received: November 10, 2016 Accepted: June 19, 2017 Published: August 07, 2017 ABSTRACT Non-small-cell lung cancer has a high mortality rate and poor prognosis. Therefore, novel therapeutic approaches are urgently needed to enhance patient survival rates. In this study, we investigated the effects of miR-21 and EZH2 on the biological behavior of human lung cancer stem cells in vitro . We found increased expression of EZH2 and miR-21 in LCSCs, and miR-21 overexpression increased EZH2 levels in LCSCs. In addition, EZH2 and miR-21 knockdown increased the sensitivity of LCSCs to chemo- and radiation therapy, and exogenous EZH2 expression rescued the effects of anti-miR-21. Cell proliferation was reduced by 39.2% and 69.7% in the presence of radio - or chemotherapy combined with anti-miR-21 transfection, respectively. The downstream molecules included Cdc2, cyclin B1, and Bcl-2, which are involved in the regulation of cell cycle and apoptosis and which could themselves be reduced or enhanced by changes in miR-21 and EZH2 levels in LCSCs. This study demonstrates the direct relationship between miR-21 and EZH2 which was increased by 43% after the application of the miR-21 mimic. Above data indicates that these two molecules can influence the biological behavior of LCSCs by altering their corresponding targets. Our findings support the potential roles of miR-21 and EZH2 in improving the therapeutic efficacy of clinical lung cancer treatments.