MiRNA-98-5p inhibits the progression of osteosarcoma by regulating cell cycle via targeting CDC25A expression.

OBJECTIVE

The aim of this study was to elucidate the exact role of microRNA-98-5p (miRNA-98-5p) in the progression of osteosarcoma and to explore its potential mechanism.

PATIENTS AND METHODS

The expression levels of miRNA-98-5p and cell division cycle 25 (CDC25A) in osteosarcoma tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, the correlation between expressions of miRNA-98-5p and CDC25A and the survival of osteosarcoma patients was analyzed. After altering miRNA-98-5p and CDC25A expressions by liposome transfection, the expression levels of CDC25A, ki67, Cyclin D1, p21, BCL2-Associated X (BAX), B-cell lymphoma-2 (BCL-2) and BCL-XL in osteosarcoma cells were detected. Subsequently, potential binding sites between miRNA-98-5p and CDC25A were predicted and further verified by miRanda and Dual-Luciferase reporter gene assay, respectively. Regulatory effects of miRNA-98-5p and CDC25A on the migratory ability of osteosarcoma cells were evaluated by transwell assay. Moreover, nude mice were subcutaneously implanted with MG-63 cells over-expressing miRNA-98-5p or negative control. In addition, the functions of miRNA-98-5p and CDC25A in tumor-bearing nude mice were explored in vivo.

RESULTS

MiRNA-98-5p was lowly expressed in osteosarcoma tissues and cell lines, whereas CDC25A was highly expressed. Survival analysis showed that the survival of osteosarcoma patients with low-level of miRNA-98-5p or high-level of CDC25A was significantly worse. Besides, a negative correlation was identified between miRNA-98-5p and CDC25A. Subsequent experiments revealed that miRNA-98-5p significantly inhibited cell cycle progression and migratory potential, whereas induced the apoptosis of osteosarcoma cells by down-regulating CDC25A.

CONCLUSIONS

MiRNA-98-5p is lowly expressed, while CDC25A is highly expressed in osteosarcoma. Furthermore, miRNA-98-5p regulates cell cycle progression by down-regulating CDC25A, thus inhibiting the progression of osteosarcoma.