Li Jingyuan, Wang Lijuan, Liu Zongzhi, Zu Chao, Xing Fanfan, Yang Pei, Yang Yongkang, Dang Xiaoqian, Wang Kunzheng
Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, P.R. China.
Department of Orthopaedics, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710068, Shaanxi Province, P.R. China.
Oncotarget. 2015 Sep 22;6(28):26216-29. doi: 10.18632/oncotarget.4460.
Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.
越来越多的证据表明,微小RNA(miRNA)失调可能通过影响细胞增殖和侵袭,促进软骨肉瘤的肿瘤生长和转移。在本研究中,我们旨在探讨miRNA在软骨肉瘤发生发展中的作用。在此,通过对软骨肉瘤组织和细胞以及软骨组织和细胞进行miRNA表达谱比较,我们发现miR-494在软骨肉瘤患者组织和软骨肉瘤癌细胞系中是一种普遍下调的miRNA,上调miR-494可在体内和体外抑制软骨肉瘤癌细胞的增殖和侵袭。此外,我们的数据表明,SOX9作为软骨分化过程的关键调节因子,是miR-494在软骨肉瘤细胞中的直接靶点和功能介质。下调SOX9也可抑制软骨肉瘤细胞的迁移和侵袭。最后,我们发现miR-494低表达与软骨肉瘤患者的总体生存率低和预后不良显著相关。因此,miR-494可能是软骨肉瘤新的共同治疗靶点和预后生物标志物。