Liu Xiaozhou, Liu Yunlai, Wu Sujia, Shi Xin, Li Lihong, Zhao Jianning, Xu Haidong
Department of Orthopedics of Jinling Hospital (Nanjing), School of Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Cell Biochem Biophys. 2014 Sep;70(1):215-24. doi: 10.1007/s12013-014-9885-8.
Osteosarcoma is the most common primary bone tumor. Recent data indicated miRNAs may be involved in the pathogenesis of osteosarcoma, suggesting some novel targets for therapy. It is known that miR-429 is down-regulated and functions as a tumor suppressor by targeting c-myc and PLGG1 in gastric and breast cancer. However, the exact role of miR-429 in osteosarcoma remained unknown. In our study, we found MiR-429 was down-regulated in primary osteosarcoma lesion and osteosarcoma cell lines. Moreover, MiR-429 can inhibit the proliferation of osteosarcoma cell lines and induce more cell apoptosis. Also, we discovered MiR-429 plays a role in osteosarcoma by binding the 3'UTR of zinc finger E-box-binding homeobox 1 (ZEB1) mRNA, and that overexpression of ZEB1 could reverse the proliferation, subsequently blocking effect of miR-429. In conclusion, miR-429 serves as a tumor suppressor via interaction with ZEB1. Our finding may provide a new target for osteosarcoma therapy.
骨肉瘤是最常见的原发性骨肿瘤。近期数据表明，微小RNA（miRNA）可能参与骨肉瘤的发病机制，提示了一些新的治疗靶点。已知miR-429在胃癌和乳腺癌中表达下调，并通过靶向c-myc和PLGG1发挥肿瘤抑制作用。然而，miR-429在骨肉瘤中的确切作用仍不清楚。在我们的研究中，我们发现miR-429在原发性骨肉瘤病变和骨肉瘤细胞系中表达下调。此外，miR-429可抑制骨肉瘤细胞系的增殖并诱导更多细胞凋亡。而且，我们发现miR-429通过结合锌指E盒结合同源框1（ZEB1）mRNA的3'非翻译区（3'UTR）在骨肉瘤中发挥作用，并且ZEB1的过表达可逆转miR-429的增殖抑制作用。总之，miR-429通过与ZEB1相互作用发挥肿瘤抑制作用。我们的发现可能为骨肉瘤治疗提供新的靶点。
