Purpose: Accumulating studies showed that the expression of microRNAs (miRNAs) was dysregulated in osteosarcoma (OS). In this study, we sought to investigate the effect of let-7a on OS progression and its potential molecular mechanism.
Patients and methods: Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression level of let-7a and Aurora-B (AURKB) in OS tissues and cells. The OS cells were treated with let-7a mimic, let7a inhibitor, negative mimic and Lv-AURKB combined with let-7a. The ability of cell proliferation, migration and invasion was measured using Cell Counting Kit-8 (CCK-8) and wound-healing and transwell invasion assays. The protein of AURKB, NF-κβp65, MMP2 and MMP9 was measured by Western blot analysis. Xenograft model was performed to investigate the effects of let-7a on tumor growth and metastasis. The lung metastasis was measured by counting the metastatic node using H&E staining.
Results: Let-7a expression was significantly underexpressed in OS cell lines and tissues compared with human osteoblast cell lines, hFOB1.19, and adjacent normal bone tissues. Exogenous let-7a inhibited the viability, migratory and invasive ability of OS cells in vitro. In addition, the overexpression of AURKB in OS cells could partly rescue let-7a-mediated tumor inhibition. Also, the overexpression of let-7a inhibited OS cell growth and lung metastasis in vivo. Furthermore, the results showed that let-7a could decrease the expression of NF-κβp65, MMP2 and MMP9 proteins by targeting AURKB in OS cells.
Conclusion: Let-7a inhibits the malignant phenotype of OS cells by targeting AURKB at least partially. Targeting let-7a and AURKB/NF-κβ may be a novel therapeutic strategy for the treatment of OS.
Keywords: Aurora-B; let-7a; malignant phenotype; osteosarcoma.