Chen Bingpeng, Liu Jingjing, Qu Ji, Song Yang, Li Yuxiang, Pan Su
1 Department of Orthopedics, The Second Hospital of Jilin University, Changchun, P.R. China.
2 Department of Oncology, Jilin Provincial Tumor Hospital, Changchun, P.R. China.
Tumour Biol. 2017 Jul;39(7):1010428317703841. doi: 10.1177/1010428317703841.
Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.
miR-25的表达改变作为癌基因或肿瘤抑制因子与许多人类恶性肿瘤进展有关。然而，miR-25在骨肉瘤进展中的确切作用仍不清楚。本研究旨在探讨miR-25在骨肉瘤中的作用及潜在机制。在本研究中，我们证明miR-25在骨肉瘤细胞系和组织中显著下调，且较低的miR-25与肿瘤-淋巴结-转移晚期及淋巴结转移相关。然后，我们发现引入miR-25显著抑制骨肉瘤细胞的体外增殖、集落形成、迁移和侵袭，并在体内抑制肿瘤生长。进一步研究表明，上皮-间质转化相关转录因子SOX4（SRY相关高迁移率族盒4）是miR-25的直接靶基因，这通过生物信息学分析预测和荧光素酶报告基因检测得到证实。此外，miR-25可降低SOX4水平的表达并抑制上皮-间质转化过程。在骨肉瘤组织中，miR-25的水平与SOX4表达水平呈负相关。SOX4过表达挽救了miR-25诱导的对骨肉瘤细胞增殖、迁移和侵袭的抑制作用。综上所述，这些结果表明miR-25通过抑制SOX4在骨肉瘤进展中发挥肿瘤抑制作用。
