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, MDK and 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. ABSTRACT: 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 tested miR‐188 expression in clinical samples of lung cancer patients, and a low expression profile of miR‐188 was found. Next, we analysed the role of miR‐188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we used a xenograft model to validate the capability of miR‐188 in tumorigenesis. Overexpression of miR‐188 reduced viability and metastasis of cancer stem cells. Similar results were reproduced in vivo, where overexpression of miR‐188 retarded tumour growth in mice. We also identified MDK as a target of miR‐188, and overexpression of MDK was found in lung cancer samples. Overexpressed MDK promoted 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 that miR‐188 inhibits 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.