Jiashi Wang, Chuang Qiu, Zhenjun Zhang, Guangbin Wang, Bin Li, Ming He
Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
Aging (Albany NY). 2018 Jun 10;10(6):1294-1305. doi: 10.18632/aging.101468.
Osteosarcoma is an aggressive bone tumor primarily affecting children and adolescents. Its cause is not yet fully understood, and there is an urgent need for more effective treatment. In the present study we identified several miRNAs whose expression is altered in osteosarcoma compared to adjacent normal tissue. Moreover, expression levels of one of those miRNAs, miR-506-3p, correlated negatively with expression of RAB3D (a Ras-related protein). Suppression of miR-506-3p in osteosarcoma led to increased expression of RAB3D, which in turn led to increased CDK4 (cyclin-dependent kinase 4) and MMP9 (matrix metalloprotein 9) activities. Our results suggest that miR-506-3p acts as a tumor suppressor in osteosarcoma and that its downregulation leads to tumor cell proliferation and metastasis due to upregulation of RAB3D- and CDK4-mediated signaling. miR-506-3p thus appears be a potentially useful target for adjuvant therapy in osteosarcoma patients.
骨肉瘤是一种侵袭性骨肿瘤，主要影响儿童和青少年。其病因尚未完全明确，因此迫切需要更有效的治疗方法。在本研究中，我们鉴定出了几种与相邻正常组织相比在骨肉瘤中表达发生改变的miRNA。此外，其中一种miRNA，即miR-506-3p的表达水平与RAB3D（一种Ras相关蛋白）的表达呈负相关。在骨肉瘤中抑制miR-506-3p会导致RAB3D表达增加，进而导致细胞周期蛋白依赖性激酶4（CDK4）和基质金属蛋白酶9（MMP9）的活性增加。我们的结果表明，miR-506-3p在骨肉瘤中起肿瘤抑制作用，其下调由于RAB3D和CDK4介导的信号上调而导致肿瘤细胞增殖和转移。因此，miR-506-3p似乎是骨肉瘤患者辅助治疗的一个潜在有用靶点。
