Upregulation of miRNA-154-5p prevents the tumorigenesis of osteosarcoma.
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS.


METHODS
The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5.


RESULTS
The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model.


CONCLUSION
These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.
['Tian|Qing|Q|', 'Gu|Yufan|Y|', 'Wang|Feifei|F|', 'Zhou|Lijun|L|', 'Dai|Zhipeng|Z|', 'Liu|Hongjian|H|', 'Wu|Xuejian|X|', 'Wang|Xinxing|X|', 'Liu|Yong|Y|', 'Chen|Songfeng|S|', 'Han|Qicai|Q|']
D000818:Animals D017209:Apoptosis D001859:Bone Neoplasms D002465:Cell Movement D049109:Cell Proliferation D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D009361:Neoplasm Invasiveness D012516:Osteosarcoma D015854:Up-Regulation D023041:Xenograft Model Antitumor Assays
Tumorigenesis Osteosarcoma microRNA-154-5p E2F5