Abstract
MicroRNAs have crucial roles in development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-124 was down-regulated in many cancers; however, the role of miR-124 in osteosarcoma development is unkonwn. In this study, we demonstrate that expression of miR-124 is significantly downregulated in osteosarcoma tissues and cell lines, compared to the adjacent tissues. The expression of miR-124 in the metastases osteosarcoma tissues was lower than that in non- metastases tissues. We identified and confirmed Rac1 as a novel, direct target of miR-124 using prdiction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed Rac1 protein expression and attenuated cell proliferation, migration, and invasion and induced apotosis in MG-63 and U2OS in vitro. Moreover, overexpression of Rac1 in miR-124-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion caused by miR-124. Therefore, our results demonstrate that miR-124 is a tumor suppressor miRNA and suggest that this miRNA could be a potential target for the treatment of osteosarcoma in future.
Highlights
Osteosarcoma is the most common primary malignant bone tumor with high morbidity in young adults and adolescents [1]
30% of those diagnosed with osteosarcoma do not survive for more than 5 years and approximately 80% of patients eventually develop metastatic disease after surgical treatment, pulmonary metastasis of osteosarcoma patients is the major cause of feral outcome [3,4]
We found that miR-124 was downregulated in osteosarcoma cell lines and primary tumor samples, and miR-124 was further identified to be a tumor suppressor, as restoration of miR-124 expression in osteosarcoma cell lines was able to inhibit cell proliferation, promote cell cycle, and suppress cell invasion and metastasis by targeting Rac1
Summary
Osteosarcoma is the most common primary malignant bone tumor with high morbidity in young adults and adolescents [1]. Though miRNAs were first discovered to have crucial functions in Caenorhabditis elegans development, recent progress in cancer biology has shown that miRNAs are frequently dysregulated in diverse cancer subtypes including breast cancer, gastric cancer, lung cancer and hepatocellular carcinoma [6]. MiR-124 has been reproted to be down-regulated in some types of cancer, such as gastric cancer, breast cancer, hepatocellular carcinoma and glioblastoma [11,12,13,14]. In these malignancies, forced expression of miR-124 inhibits cancer cell growth. Our date suggest important roles of miR-124 in osteosarcoma pathogenesis and indicate its potential application in cancer therapy
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