Let-7b inhibits the malignant behavior of glioma cells and glioma stem-like cells via downregulation of E2F2

Abstract

Glioblastoma multiforme (GBM), the most common and lethal primary brain tumor in adults characterized by high proliferative ability and mortality rate, contains a small subpopulation of cancer stem-like cells (CSCs), which is responsible for GBM progression and therapeutic resistance. Numerous microRNAs are strongly implicated in the malignancy of glioma. However, their specific functions and roles have yet to be fully demonstrated. In the present study, we revealed that the upregulation of Let-7b, a member of the Let-7 microRNA family, inhibited proliferation, migration, and invasion in glioma cell lines. Using bioinformatics, expression analysis, and luciferase assay, E2F2 was confirmed as a candidate target of Let-7b. Moreover, we also observed that elevated levels of Let-7b resulted in a reduction of tumor sphere growth and stemness of glioma stem-like cells. Furthermore, we found that knockdown of E2F2 expression could reduce the proliferation of glioma and GSCs, while overexpression of E2F2 partially abrogated the inhibitory effect of Let-7b on the proliferation of glioma and GSCs. In conclusion, we suggest that Let-7b could be developed into a promising anticancer target in glioma.

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