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

Lung Cancer
28/06/2020

Yang X, et al. Exp Physiol 2020.

ABSTRACT

NEW FINDINGS: What is the central question of this study? To probe the function of miR-188 in biological characteristics of lung cancer stem cells and the mechanical molecules involved. What is the main finding and its importance? This study highlights a novel molecular mechanism involving miR-188, MDP and the Hippo signaling pathway which plays a suppressive role in biological activity of lung cancer stem cells. This finding may offer novel 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 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 analyzed the role of miR-188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we employed 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 tumor growth in mice. Meanwhile, we identified MDK as a target of miR-188, and over-expression of MDK was found in lung cancer samples. Overexpressed MDK promoted the malignant behaviors of lung cancer stem cells. In addition, the Hippo pathway was found inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumors. To sum up, our results reveal that miR-188 inhibits the malignant behaviors of lung cancer stem cells as well as the growth of xenograft tumors. This study may offer novel insights into gene-based therapies for cancer. This article is protected by copyright. All rights reserved.