Downregulation of miRNA-146a-5p promotes malignant transformation of mesenchymal stromal/stem cells by glioma stem-like cells
Xingliang Dai, Yunfei Wang, Xuchen Dong, Minfeng Sheng, Haiyang Wang, Jia Shi, Yujing Sheng, Liang Liu, Qianqian Jiang, Yanming Chen, Bingshan Wu, Xuejun Yang, Hongwei Cheng, Chunsheng Kang, Jun Dong
Abstract
using dual-color fluorescence tracing. Cell sorting and micropipetting techniques were used to obtain highly proliferative MSC monoclones from each model, and these cells were identified as transformed MSC lines 1, 2 and 3. Nineteen miRNAs were upregulated and 24 miRNAs were downregulated in all three transformed MSC lines compared to normal BMSCs. Reduced miR-146a-5p expression in the transformed MSCs was associated with their proliferation, malignant transformation and overexpression of heterogeneous nuclear ribonucleoprotein D. These findings suggest that downregulation of miR-146a-5p leads to overexpression of its target gene, heterogeneous nuclear ribonucleoprotein D, thereby promoting malignant transformation of MSCs during interactions with GSCs. Given the risk that MSCs will undergo malignant transformation in the glioma microenvironment, targeted glioma therapies employing MSCs as therapeutic carriers should be considered cautiously.