microRNA-188 inhibits biological activity of lung cancer stem cells through targeting MDK and mediating the Hippo pathway.

New Findings What is the central question of this study?The aim was to investigate the function of microRNA-188 in the biological characteristics of lung cancer stem cells and the molecular mechanisms involved. What is the main finding and its importance?This study highlights a new molecular mechanism involving microRNA-188,MDKand the Hippo signalling pathway that plays a suppressive role in biological activity of lung cancer stem cells. This finding might offer new insights into gene-based therapy for lung cancer. MicroRNAs (miRNAs) have been implicated in lung cancer and reported as new promising diagnostic and therapeutic tools for cancer control. Here, we investigated the action of microRNA-188 (miR-188) in lung cancer stem cells. We first testedmiR-188expression in clinical samples of lung cancer patients, and a low expression profile ofmiR-188was found. Next, we analysed the role ofmiR-188in lung cancer stem cells with cell growth assays. To verify thein vitroresults, we used a xenograft model to validate the capability ofmiR-188in tumorigenesis. Overexpression ofmiR-188reduced viability and metastasis of cancer stem cells. Similar results were reproducedin vivo, where overexpression ofmiR-188retarded tumour growth in mice. We also identifiedMDKas a target ofmiR-188, and overexpression ofMDKwas found in lung cancer samples. OverexpressedMDKpromoted the malignant behaviours of lung cancer stem cells. In addition, the Hippo pathway was found to be inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of the Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumours. To sum up, our results reveal thatmiR-188inhibits the malignant behaviours of lung cancer stem cells and the growth of xenograft tumours. This study might offer new insights into gene-based therapies for cancer.