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.
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.
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.
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.
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.
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.