Research Paper Volume 12, Issue 10 pp 9151—9172
Downregulation of miRNA-146a-5p promotes malignant transformation of mesenchymal stromal/stem cells by glioma stem-like cells
- 1 Brain Tumor Lab, Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- 2 Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
- 3 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
Received: November 3, 2019 Accepted: March 9, 2020 Published: May 25, 2020
https://doi.org/10.18632/aging.103185How to Cite
Copyright © 2020 Dai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Mesenchymal stromal/stem cells (MSCs) are promising carriers in cell-based therapies against central nervous system diseases, and have been evaluated in various clinical trials in recent years. However, bone marrow-derived MSCs (BMSCs) are reportedly involved in tumorigenesis initiated by glioma stem-like cells (GSCs). We therefore established three different orthotopic models of GSC-MSC interactions in vivo 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.
Abbreviations
GSCs: glioma stem-like cells; MSCs: mesenchymal stromal/stem cells; RFP: red fluorescent protein; EGFP: enhanced green fluorescent protein; tMSCs: transformed MSCs; FISH: fluorescence in situ hybridization.