miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2).
MicroRNAs are short regulatory RNAs that play crucial roles in cancer development and progression. MicroRNA-646 (miR-646) is downregulated in many human cancers, and increasing evidence indicates that it functions as a tumor suppressor. However, the role of miR-646 in osteosarcoma remains unclear. Expression levels of miR-646 in osteosarcoma cell lines and patient tissues were evaluated by quantitative real-time PCR (qRT-PCR), and the clinicopathological significance of the resultant data was later analyzed. Next, we investigated the role of miR-646 to determine its potential roles on osteosarcoma cell proliferation, migration, and invasion in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-646, and the results were validated in the osteosarcoma cell line. In this study, we found that miR-646 was downregulated in osteosarcoma cell lines and osteosarcoma tissues compared with normal osteoblast cell line NHOst and paired adjacent nontumor tissue. We found that a lower expression of miR-646 was associated with metastasis. In osteosarcoma cells, overexpression of miR-646 inhibited cell proliferation, migration, and invasion. In contrast, downregulation of miR-646 expression promoted osteosarcoma cell proliferation, migration, and invasion. Next, we identified that the FGF2 gene is a novel direct target of miR-646 in osteosarcoma cells. Moreover, enforced expression of FGF2 partially reversed the inhibition of cell proliferation, migration, and invasion that was caused by miR-646. Our study demonstrated that miR-646 might be a tumor suppressor in osteosarcoma via the regulation of FGF2, which provided a potential prognostic biomarker and therapeutic target.
Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Weihui, 453100, China, xiaohuisun14@163.com.
Xiao-hui
XH
Sun
Xiao-lin
XL
Geng
Jun
J
Zhang
Chao
C
Zhang
D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology
D035683:MicroRNAs; D016222:Fibroblast Growth Factor 2