Xia Hui, Zhang Wen, Zhang Baoshi, Zhao Yingnan, Zhao Yunlong, Li Shaojun, Liu Yang
Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing, China.
Department of Thoracic Surgery, PLA General Hospital, Beijing, China.
Oncotarget. 2017 Aug 7;8(49):85442-85451. doi: 10.18632/oncotarget.20006. eCollection 2017 Oct 17.
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 . 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.
非小细胞肺癌死亡率高且预后较差。因此,迫切需要新的治疗方法来提高患者生存率。在本研究中,我们调查了miR-21和EZH2对人肺癌干细胞生物学行为的影响。我们发现肺癌干细胞中EZH2和miR-21表达增加,且miR-21过表达会提高肺癌干细胞中EZH2的水平。此外,EZH2和miR-21基因敲低增加了肺癌干细胞对化疗和放疗的敏感性,外源性EZH2表达可挽救抗miR-21的作用。在联合抗miR-21转染的放疗或化疗存在的情况下,细胞增殖分别降低了39.2%和69.7%。下游分子包括Cdc2、细胞周期蛋白B1和Bcl-2,它们参与细胞周期和凋亡的调控,并且其自身可因肺癌干细胞中miR-21和EZH2水平的变化而降低或升高。本研究证明了miR-21与EZH2之间的直接关系,在应用miR-21模拟物后这种关系增加了43%。上述数据表明这两个分子可通过改变其相应靶点来影响肺癌干细胞的生物学行为。我们的研究结果支持miR-21和EZH2在提高临床肺癌治疗疗效方面的潜在作用。