MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1

MicroRNA-493通过直接靶向特异性蛋白1抑制骨肉瘤细胞增殖和侵袭

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作者:Ming Qian, Haiyi Gong, Xinghai Yang, Jian Zhao, Wangjun Yan, Yan Lou, Dongyu Peng, Zhenxi Li, Jianru Xiao

Abstract

Osteosarcoma (OS) is the most common type of primary bone tumor and accounts for ~60% of all malignant bone tumors in children and adolescents. A large number of studies have proposed that the dysregulated and dysfunctional microRNAs may serve important roles in the occurrence, progression and metastasis of various types of human cancer, including OS. MicroRNA-493 (miR-493) has been identified to act as a tumor suppressor in several types of human cancer. However, little is known regarding the expression pattern and clinical significance of miR-493 in OS. In the present study, reverse transcription-quantitative polymerase chain reaction analysis revealed that miR-493 was markedly downregulated in OS tissues and cell lines and a low miR-493 level were associated with distant metastasis and clinical stage. Furthermore, functional experiments demonstrated that enforced expression of miR-493 led to a significant decrease in OS cell proliferation and invasion in vitro. Furthermore, through bioinformatics analysis, specificity protein 1 (SP1) was identified as a direct target gene of miR-493 in OS. Its expression was upregulated in OS tissues and was negatively associated with miR-493 expression levels. Inhibition of SP1 expression also suppressed the proliferation and invasion of OS, exerting a similar effect to that induced by miR-493 overexpression. These results suggested that miR-493 inhibited OS cell proliferation and invasion through negative regulation of SP1. Therefore, miR-493/SP1 may represent a potential therapeutic target for the treatment of OS.

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