期刊
AGING-US
卷 12, 期 13, 页码 13647-13667出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103489
关键词
glioma stem-like cells (GSCs); mesenchymal stem cells (MSCs); cell fusion; tumor microenvironment (TME); miR-146b-5p; SMARCA5
资金
- National Natural Science Foundation of China [81702457]
- Research and Practice Innovation Program for Postgraduates in Jiangsu [KYCX19_1982]
- Clinical Special Disease Diagnosis and Treatment Technology in Suzhou, China [LCZX201807]
Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-beta pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-beta pathway.
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