Zhao Fuyou, Lv Jie, Gan Huaiyong, Li Yumei, Wang Ri, Zhang Haoran, Wu Qiong, Chen Yuqing
Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College Bengbu, Anhui 233000, China.
Department of Microbiology, Bengbu Medical College Bengbu, Anhui 233000, China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1451-8. eCollection 2015.
microRNAs (miRNA) are regulators of gene expression, but little is known about miRNA expression profiles in stem cells of osteosarcoma (OS). C117 and Stro-1 are known stem cell markers of OS. In the study, CD117 and stro-1 positive (CD117(+)stro-1(+)) and CD117 and stro-1 negative (CD117(-)stro-1(-)) cells were isolated from MG63 cells CD117(+)stro-1(+) cells showed more metastatic ability and stem cell formation rate than CD117(-)stro-1(-) ones. To find the difference between CD117(+)stro-1(+) and CD117(-)stro-1(-) cells, the miRNA expression profile was examined using DNA microarray. MicroRNAs were differentially expressed in osteosarcoma cells with CD117(+)stro-1(+) and CD117(-)stro-1(-). The significant miRNAs included miR-15a, miR-302a, miR-423-5p, miR-1247, miR-1243 and others, which were confirmed by real time RT-PCR. The significant down-regulated miR-1247 was confirmed that was a potential tumor suppressor by targeting MAP3K9. Our results indicated that dysregulation of miRNAs is involved in osteosarcoma and miR-1247 plays an important role in progression of osteosarcoma.
微小RNA(miRNA)是基因表达的调节因子,但骨肉瘤(OS)干细胞中的miRNA表达谱却鲜为人知。C117和Stro-1是已知的骨肉瘤干细胞标志物。在本研究中,从MG63细胞中分离出CD117和Stro-1阳性(CD117(+)Stro-1(+))及CD117和Stro-1阴性(CD117(-)Stro-1(-))细胞。CD117(+)Stro-1(+)细胞比CD117(-)Stro-1(-)细胞表现出更强的转移能力和干细胞形成率。为了找出CD117(+)Stro-1(+)和CD117(-)Stro-1(-)细胞之间的差异,使用DNA微阵列检测了miRNA表达谱。在骨肉瘤细胞中,CD117(+)Stro-1(+)和CD117(-)Stro-1(-)细胞中的miRNA存在差异表达。显著差异的miRNA包括miR-15a、miR-302a、miR-423-5p、miR-1247、miR-1243等,这些通过实时RT-PCR得到了证实。显著下调的miR-1247被证实通过靶向MAP3K9是一种潜在的肿瘤抑制因子。我们的结果表明,miRNA的失调与骨肉瘤有关,且miR-1247在骨肉瘤进展中起重要作用。