Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.
Department of Pain Management, the Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China.
Biosci Rep. 2018 Jan 19;38(1). doi: 10.1042/BSR20171017. Print 2018 Feb 28.
Ewing sarcoma (EWS) is a kind of aggressive tumor of bone and soft tissues, which most occurring in children and adolescents. MicroRNAs (miRNAs) perform essential function in the progression and development of EWS, while the putative role of miR-638 in EWS remains uncertain. Accordingly, we detected the expression of miR-638 and explored its putative biological effects on the malignant phenotype of EWS cells. As expected, miR-638 was significantly down-regulated in EWS cells. Moreover, overexpression of miR-638 suppressed cell growth, induced cell apoptosis, and inhibited tubule formation of EWS cells Among the putative target genes of miR-638 predicted by the miRNA target prediction tools, vascular endothelial cell growth factor A (VEGFA) attracted out attention most. The luciferase reporter assays reaffirmed that VEGFA was a targeted gene of miR-638 in EWS cells. Furthermore, miR-638 suppressed the mRNA and protein level of VEGFA, and restored the expression of VEGFA reversed the suppressed effects of miR-638 in EWS cells. Taken together, the results suggested that miR-638 might perform tumor suppressive effects in EWS, which might be mediated, at least partially, through suppressing the activity of VEGFA.
尤因肉瘤（EWS）是一种侵袭性的骨和软组织肿瘤，主要发生在儿童和青少年。microRNAs（miRNAs）在 EWS 的进展和发展中发挥着重要作用，而 miR-638 在 EWS 中的潜在作用尚不清楚。因此，我们检测了 miR-638 的表达，并探讨了其对 EWS 细胞恶性表型的潜在生物学效应。正如预期的那样，miR-638 在 EWS 细胞中显著下调。此外，miR-638 的过表达抑制细胞生长，诱导细胞凋亡，并抑制 EWS 细胞的管形成。在 miRNA 靶预测工具预测的 miR-638 的潜在靶基因中，血管内皮细胞生长因子 A（VEGFA）最引起我们的注意。荧光素酶报告基因检测进一步证实 VEGFA 是 EWS 细胞中 miR-638 的靶基因。此外，miR-638 抑制 VEGFA 的 mRNA 和蛋白水平，恢复 VEGFA 的表达逆转了 miR-638 在 EWS 细胞中的抑制作用。综上所述，结果表明 miR-638 可能在 EWS 中发挥肿瘤抑制作用，至少部分通过抑制 VEGFA 的活性来介导。
