HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway
HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway
复制标题
DOI：
10.1016/j.gene.2018.11.081
复制
发表时间：
2019-03-20
期刊：
影响因子：
3.5
通讯作者：
Wang, Yu-Liang
中科院分区：
文献类型：
--
作者：
Chen, Yan-Qiang;Yang, Tong-Qun;Wang, Yu-Liang
骨肉瘤是儿童和青少年最常见的恶性骨肿瘤。HOXA5的异常表达导致多种疾病，包括癌症。然而，HOXA5在骨肉瘤中的具体功能和分子机制尚不完全清楚。在本研究中，我们重点研究了HOXA5在体外U2OS和MG63细胞中的作用。我们观察到HOXA5在U2OS、MG63和SaOS2人骨肉瘤细胞中的表达低于hFOB1.19人骨母细胞。HOXA5在U2OS和MG63细胞中过表达，显著降低细胞存活和增殖，升高细胞凋亡和caspase-3活性。HOXA5也通过增加p53激活p38 α MAPK通路。与pcDNA3.1-HOXA5组相比，用p53抑制剂α -pifithan或p38 α MAPK抑制剂SB203580处理U2OS和MG63细胞可提高细胞存活率和增殖，降低细胞凋亡。综上所述，我们的研究表明p53和p38 α MAPK信号轴促进了HOXA5抑制骨肉瘤细胞生长和刺激细胞凋亡的作用。
Osteosarcoma is the most common malignant bone tumor in children and adolescents. Aberrant expression of HOXA5 results in various diseases, including cancers. However, the specific function and molecular mechanism of HOXA5 in osteosarcoma is not fully understood. In the present study, we focused on HOXA5 in U2OS and MG63 cells in vitro. We observed lower expression of HOXA5 in U2OS, MG63, and SaOS2 human osteosarcoma cells, compared with hFOB1.19 human osteoblastic cells. HOXA5 overexpression in U2OS and MG63 cells markedly reduced cell survival and proliferation and elevated cell apoptosis and caspase-3 activity. HOXA5 also activated the p38 alpha MAPK pathway by increasing p53. Treating U2OS and MG63 cells with the p53 inhibitor alpha-pifithan or the p38 alpha MAPK inhibitor SB203580 led to higher cell survival and proliferation and lower cell apoptosis, compared with the pcDNA3.1-HOXA5 group. In conclusion, our study showed that the p53 and p38 alpha MAPK signal axis facilitated HOXA5's role in inhibiting growth and stimulating apoptosis of osteosarcoma cells.