MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively.
MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively.
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miR-193a-3p 和 miR-193a-5p 分别通过下调 Rab27B 和 SRR 抑制人骨肉瘤细胞的转移。
DOI：
10.1007/s10585-016-9783-0
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发表时间：
2016-04
影响因子：
4
通讯作者：
Cai S
中科院分区：
文献类型：
--
作者：
Pu Y;Zhao F;Cai W;Meng X;Li Y;Cai S
MicroRNAs在骨肉瘤的发生和发展中起着关键作用，骨肉瘤是最常见的原发骨恶性肿瘤。基于测序的miR-193a-3p和miR-193a-5p在高转移骨肉瘤细胞系(MG63.2)启动子区域的甲基化导致miR-193a-3p和miR-193a-5p在高转移骨肉瘤细胞系(MG63.2)中的表达较低转移骨肉瘤细胞系(MG63)的表达降低。进一步的伤口愈合和侵袭实验表明，miR-193a-3p和miR-193a-5p均抑制骨肉瘤细胞的迁移和侵袭。此外，将miR-193a-3p和miR-193a-5p模拟物导入MG63.2细胞或将抗原体导入MG63细胞证实了它们在骨肉瘤转移中的关键作用。此外，生物信息学预测和生化分析结果清楚地表明，分泌型小GTP酶Rab27B和丝氨酸消旋酶(SRR)分别是miR-193a-3p和miR-193a-5p的直接靶标。这两个靶点确实参与了miR-193a-3p和miR-193a-5p诱导的抑制骨肉瘤细胞迁移和侵袭的作用。MiR-193a-3p和miR-193a-5p通过下调Rab27B和SRR基因在骨肉瘤转移中发挥重要作用，因此可能成为诊断骨肉瘤的有用生物标志物和治疗转移性骨肉瘤的潜在候选基因。
MicroRNAs have been identified as key players in the development and progression of osteosarcoma, which is the most common primary malignancy of bone. Sequencing-based miR-omic and quantitative real-time PCR analyses suggested that the expression of miR-193a-3p and miR-193a-5p was decreased by DNA methylation at their promoter region in a highly metastatic osteosarcoma cell line (MG63.2) relative to their expression in the less metastatic MG63 cell line. Further wound-healing and invasion assays demonstrated that both miR-193a-3p and miR-193a-5p suppressed osteosarcoma cell migration and invasion. Moreover, introducing miR-193a-3p and miR-193a-5p mimics into MG63.2 cells or antagomiRs into MG63 cells confirmed their critical roles in osteosarcoma metastasis. Additionally, bioinformatics prediction along with biochemical assay results clearly suggested that the secretory small GTPase Rab27B and serine racemase (SRR) were direct targets of miR-193a-3p and miR-193a-5p, respectively. These two targets are indeed involved in the miR-193a-3p- and miR-193a-5p-induced suppression of osteosarcoma cell migration and invasion. MiR-193a-3p and miR-193a-5p play important roles in osteosarcoma metastasis through down-regulation of the Rab27B and SRR genes and therefore may serve as useful biomarkers for the diagnosis of osteosarcoma and as potential candidates for the treatment of metastatic osteosarcoma.