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MicroRNA-4731-5p delivered by AD-mesenchymal stem cells induces cell cycle arrest and apoptosis in glioblastoma |
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| Authors: | Amir Allahverdi Ehsan Arefian Masoud Soleimani Jafar Ai Negin Nahanmoghaddam Aliakbar Yousefi-Ahmadipour Somayeh Ebrahimi-Barough |
| Institution: | 1. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Molecular and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran;2. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran;3. Hematology and Cell therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;4. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Pediatrics, School of Medicine, Bouali Childrens' Hospital, Ardabil University of Medical Sciences, Ardabil, Iran;6. Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran |
| Abstract: | Glioblastoma multiforme (GBM) exhibits the most malignant brain tumor with very poor prognosis. MicroRNAs (miRNAs) are regulatory factors that can downregulate the expression of multiple genes. Several miRNAs acting as tumor-suppressor genes have been identified so far. The delivery of miRNA by mesenchymal stem cell (MSC) due to their ability to specifically target tumors is a new, hopeful therapeutic approach for glioblastoma. The objective of our study is the investigation of the effect of lentivirus-mediated microRNA-4731 (miR-4731) genetic manipulated adipose-derived (AD)-MSC on GBM. The downregulation of miR-4731 in human GBM tumor was detected using the GEO dataset. To evaluate the function of miR-4731, we overexpressed miR-4731 using lentiviral vectors in U-87 and U-251 GBM cell lines. The effects of miR-4731 on cell proliferation and cell cycle of glioma cells were analyzed by wound test and flow-cytometry assay. miR-4731 inhibited the proliferation of GBM cancer cells. Coculturing was used to study the antiproliferative effect of miR-4731-AD-MSCs on GBM cell lines. Direct and indirect coculture of GBM cell lines with miR-4731-AD-MSCs induced cell cycle arrest and apoptosis. Our findings suggest that AD-MSCs expressing miR-4731 have favorable antitumor characteristics and should be further explored in future glioma therapy. |
| Keywords: | apoptosis delivery vehicle gene therapy glioblastoma human adipose-derived mesenchymal stem cells microRNA |