miR-182-5p Inhibits NKAPL Expression and Promotes the Proliferation of Osteosarcoma

Purpose: Osteosarcoma, a malignant bone tumor, has the lowest survival rate among all pediatric cancers. NF-κB-activating protein-like (NKAPL) is highly homologous with NKAP. The expression of NKAPL is downregulated in primary liver cancer and breast cancer, and plays a role of tumor suppressor gene. However, the role of NKAPL in osteosarcoma has not been reported. Materials and Methods: We explored the effect of NKAPL on the proliferation of osteosarcoma cells by immunohistochemical, RT-PCR, Western blot, and double luciferase reporter gene analysis. Results: The low expression of NKAPL mRNA was correlated with distant metastasis (P = 0.017), tumor size (P = 0.023), and clinical stage (P < 0.001). The NKAPL expression level in MG63 and U2OS cells was lower than that in Nhost cells. Downregulation of NKAPL expression in Nhost cells could promote cell proliferation and upregulation of NKAPL expression in MG63 and U2OS cells could inhibit cell proliferation. miR-182-5p expression was negatively correlated with NKAPL mRNA expression (R = 0.1169, P = 0.0099). After upregulating NKAPL expression, the Notch1, hes1, hey2, and cyclin D1 expression levels were significantly decreased, with G0/G1 phase arrest and G2/M phase reduction. Conclusions: miR-182-5p targeted NKAPL and inhibit NKAPL expression in osteosarcoma. miR-182-5p could regulate cell cycle and promote tumor proliferation through upregulating Notch signaling pathway.