Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-l Axis

Background: Tanshinone IIA (TIIA) is one of the active constituents derived from the rhizome of Danshen, a traditional Chinese herbal. Recently, microRNAs (miRNAs) have been suggested to be associated with the anticancer role of TIIA. However, it remains vague of the interaction between miRNAs and TIIA in glioma, a common aggressive brain tumor in humans. Methods: Expression of miRNA (miR)-16-5p and talin-1 (TLN1) was detected using reverse transcription-quantitative polymerase chain reaction and Western blotting. Cell proliferation, migration and invasion were assessed with cell viability assay, transwell assay, Western blotting, and xenograft tumor experiment. The target binding between miR-16-5p and TLNl was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results: TIIA treatment inhibited cell viability, migration and invasion, and decreased Cyclin D1, matrix metalloproteinase (MMP)-9 and Vimentin expression in glioma T98G and A172 cells both in vitro and in vivo. Thus, TIIA induced anti-glioma role, wherein miR-16-5p was upregulated and TLN1 was downregulated. Moreover, silencing miR-16-5p could abate TIIA-mediated suppression on glioma cell proliferation, migration and invasion in vitro and in vivo. TLNl overexpression also exerted tumor-promoting effect in TIIA-treated T98G and A172 cells. Mechanically, miR-16-5p could regulate TLNl expression via target binding, and depleting TLN1 could counteract the inhibitory effect of miR-16-5p knockdown on the curative effect of TIIA in T98G and A172 cells. Conclusion: TIIA exerted the anti-proliferation, anti-migration and anti-invasion role in glioma cells both in vitro and in vivo partially through regulating miR-16-5p/TLN1 axis. Keywords: tanshinone IIA, TIIA, miR-16-5p, TLN1, glioma