ATG7-mediated autophagy involves in miR-138-5p regulated self-renewal and invasion of lung cancer stem-like cells derived from A549 cells

Activation and proliferation of cancer stem cells exert an important role in the invasion, metastasis, and recurrence of malignant tumors, including lung cancer. Therefore, exploring molecular targets related to self-renewal and mobility of lung cancer stem cells has important clinical significance. In our present study, we aimed to explore the effects of miR-138-5p on lung cancer stem-like cells and associated regulatory mechanism. In our present study, enhanced self-renewal capacity and elevated expression of cancer stem cells markers CD133, CD44, aldehyde dehydrogenase 1 of lung cancer stem-like cells derived from A549 cells were firstly verified. Then, obviously enhanced autophagy was found in lung cancer stem-like cells compared with parental cells A549. Besides, we found that enhanced autophagy induced by rapamycin promoted self-renewal and cell mobility of lung cancer stem-like cells and suppression of autophagy by 3-methyladenine exerted just opposite effects. In addition, miR-138-5p was found to be downregulated in lung cancer stem-like cells compared with that in parental cell A549. At the same time, overexpression of miR-138-5p by transfected with miR-138-5p mimic was found to effectively suppress self-renewal and invasion of lung cancer stem-like cells. Further study revealed that ATG7 was a target of miR-138-5p and overexpressed miR-138-5p suppressed ATG7-mediated autophagy. In addition, specific small interference RNA-ATG7 strengthened the inhibiting effect of miR-138-5p mimic on self-renewal and invasion of lung cancer stem-like cells. Taken together, we found that autophagy helped to maintain self-renewal and invasion ability of lung cancer stem-like cells and overexpressed miR-138-5p exerted anti-tumor effects by blocking the self-renewal and invasion of lung cancer stem-like cells through suppressing ATG7-mediated autophagy.

Automated summary

Activation and proliferation of cancer stem cells play crucial roles in malignant tumors, including lung cancer, with miR-138-5p identified as a key regulator in self-renewal and invasion of lung cancer stem-like cells. Autophagy was found to be essential in maintaining self-renewal and invasion ability of lung cancer stem-like cells, with miR-138-5p suppressing ATG7-mediated autophagy to exert anti-tumor effects.