MiRNA-15a inhibits proliferation, migration and invasion by targeting TNFAIP1 in human osteosarcoma cells.
Recent data strongly suggest the important role of miRNAs in various cancer-related processes. Osteosarcoma is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In this study, the role of miRNA-15a (miR-15a) in the progression and metastasis of osteosarcoma was investigated. The result demonstrated that the expression of miR-15a was down-regulated in osteosarcoma tissues and cell lines as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. In functional assays, miR-15a inhibited cell proliferation, migration and invasion in U2OS and MG-63 cells. Meanwhile, bioinformatic analysis combined with experimental confirmation demonstrated that tumor necrosis factor; α-induced protein 1 (TNFAIP1) gene is a potential target of miR-15a and can be directly regulated by miR-15a. Down-regulation of TNFAIP1 induced effects on osteosarcoma cell lines similar to those induced by miR-15a. Taken together, these data suggest that miR-15a may act as a tumor suppressor, which is commonly down-regulated in both osteosarcoma tissues and cells. TNFAIP1 plays an important role in mediating miR-15a dependent biological functions in osteosarcoma. Reintroduction of miR-15a may be a novel therapeutic strategy by down-regulating TNFAIP1 expression.
Department of Traumatology, Tianjin Hospital Tianjin 300211, PR China.
Xu
X
Tian
Department of Traumatology, Tianjin Baodi Hospital Tianjin 301800, PR China.
Jian
J
Zhang
Department of Traumatology, Tianjin Baodi Hospital Tianjin 301800, PR China.
Liang
L
Yan
Department of Traumatology, Tianjin Hospital Tianjin 300211, PR China.
Jing-Ming
JM
Dong
Department of Traumatology, Tianjin Baodi Hospital Tianjin 301800, PR China.
Qiang
Q
Guo
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D011506:Proteins; C115968:TNFAIP1 protein, human
invasion; miRNA-15a (miR-15a); migration; osteosarcoma; proliferation; tumor necrosis factor; α-induced protein 1 (TNFAIP1)