Let-7a inhibits osteosarcoma cell growth and lung metastasis by targeting Aurora-B

Jing-Jing Yu,1,* Wen-Sen Pi,2,* Yuan Cao,3 Ai-Fen Peng,4 Zhi-Yuan Cao,2 Jia-Ming Liu,2 Shan-Hu Huang,2 Zhi-Li Liu,2 Wei Zhang1 1Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of Medical Imaging, The First Clinical Medical School of Nanchang University, Nanchang 330006, People’s Republic of China; 4College of Humanities, Jiangxi University of Traditional Chinese Medicine, Nanchang 330001, People’s Republic of China *These authors contributed equally to this work 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: let-7a, Aurora-B, osteosarcoma, malignant phenotype