Sun Yinghua, Wang Fuchao, Wang Li, Jiao Zhaode, Fang Jun, Li Jianmin
Department of Orthopedics, Yidu Central Hospital, Weifang Medical University, Weifang, Shandong 262500, P.R. China.
Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Lett. 2017 Aug;14(2):2353-2358. doi: 10.3892/ol.2017.6441. Epub 2017 Jun 21.
Osteosarcoma is the most common aggressive sarcoma of the bone in children and adolescents. It is characterized by a high level of genetic instability and recurrent DNA deletions and amplifications. microRNAs (miRNAs) play a key role in cancer initiation, progression and metastasis; however, the potential role of miRNAs in osteosarcoma remains largely unknown. In the present study, miR-433 was shown to be overexpressed in osteosarcoma tissues compared with normal human osteoblasts. Transfection of miR-433 mimics into osteosarcoma cell lines significantly decreased apoptosis by targeting programmed cell death 4, a tumor suppressor that is involved in apoptosis. In contrast, inhibition of miR-433 enhanced apoptosis. Furthermore, miR-433 overexpression inhibited the apoptosis of tumor cells and increased tumor growth. The results of the present study suggested that miR-433 is a potential molecular target for osteosarcoma therapy.
骨肉瘤是儿童和青少年中最常见的侵袭性骨肉瘤。其特征是高水平的基因不稳定性以及反复出现的DNA缺失和扩增。微小RNA(miRNA)在癌症的发生、发展和转移中起关键作用;然而,miRNA在骨肉瘤中的潜在作用仍 largely未知。在本研究中,与正常人成骨细胞相比,miR-433在骨肉瘤组织中被证明过表达。将miR-433模拟物转染到骨肉瘤细胞系中,通过靶向程序性细胞死亡4(一种参与细胞凋亡的肿瘤抑制因子)显著降低了细胞凋亡。相反,抑制miR-433可增强细胞凋亡。此外,miR-433的过表达抑制了肿瘤细胞的凋亡并促进了肿瘤生长。本研究结果表明,miR-433是骨肉瘤治疗的一个潜在分子靶点。