MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated with prognosis of osteosarcoma patients.
Recent studies have shown that microRNA-451 (miR-451) was significantly decreased in osteosarcoma tissues and was identified as a tumor suppressor in other types of human cancers. However, its clinical significance and molecular mechanisms in osteosarcoma are still not well understood. MiR-451 levels are evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in osteosarcoma cell lines and in 68 pairs of osteosarcoma and adjacent noncancerous tissues. Then, the associations of miR-451 expression with clinicopathological features of patients were determined. The effects of miR-451 in osteosarcoma cells were examined by MTT and Matrigel invasion assay. The functional target of miR-451 were determined by bioinformatics analysis and validated by luciferase reporter analyses and Western blot assay. Our results showed that the expression of miR-451 was significantly downregulated in osteosarcoma tissues compared with corresponding noncancerous tissues (P < 0.01). Particularly, statistical analysis of primary human osteosarcoma indicated that decreased expression of miR-451 was correlated with metastasis and recurrence. Moreover, the miR-451 force-expression suppressed cell proliferation and invasion in vitro. Based on bioinformatics analysis, we found that chemokine ligand 16 (CXCL16) was identified as a direct functional target of miR-451. Consistent with the effects of miR-451, silencing CXCL16 could phenocopy the effects of miR-451 on phenotypes of osteosarcoma cells. Furthermore, CXCL16 expression was upregulated in osteosarcoma tissues and inversely associated with miR-451 in human osteosarcoma tissues. Our data reveal a downregulated expression of miR-451 in osteosarcoma tissues, which is inversely associated with CXCL16 levels. These observations demonstrated that miR-451 may play an important role in tumor growth and metastasis in osteosarcoma.
Department of Orthopedics, Ningbo Development Zone Center Hospital, Ningbo, 315800, China.
Fei
F
Zhang
Wei
W
Huang
Meixia
M
Sheng
Tielong
T
Liu
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D051116:Receptors, Scavenger / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D051116:Receptors, Scavenger