These results suggest that miR-145 acts as a tumor suppressor by directly reducing expression of FLI-1, and that the miR-145/FLI-1 pathway is important for tumor progression in OS.
In this work, the main goal was centered on the development and full characterization of an efficient micellar nanosystem, based on the chemical conjugation between the amphiphilic copolymer Pluronic® L64 and the cationic polymer polyethyleneimine (PEI), to deliver the therapeutic miRNA-145 into OS cells leading to inhibition of cell proliferation and migration, and ultimately inducing cell death, crafting a novel anticancer therapeutic approach to OS.
Moreover, the expression of miR-145 was mediated by a constructed lentivirus vector to inoculate nude mice to observe the inhibiting effect of miR-145 in OS in vivo.
To the best of our knowledge, the present study demonstrates for the first time that, as a tumor suppressor, miRNA‑145 inhibits OS cell proliferation and invasion, at least in part by directly targeting ROCK1.
In the present study, miR-145 was downregulated in OS tissues and cell lines and it was shown that miR-145 expression was closely correlated with advanced tumor progression in patients of OS.
These effects were associated with decreased expression of Notch-1 and its downstream genes, such as vascular endothelial growth factor and matrix metalloproteinases, as well as increased expression of a panel of tumor-suppressive microRNAs (miRNAs), including miR-34a, miR-143, miR-145 and miR-200b/c that are typically lost in osteosarcoma.