Abstract
Osteosarcoma is the most common primary bone tumour in children and adolescents. Accumulating evidence has shown that microRNAs (miRNAs) participate in the development of almost all types of cancer. Here, we investigated the role of miR‐224 in the development and progression of osteosarcoma. We demonstrated that miR‐224 was down‐regulated in osteosarcoma cell lines and tissues. Lower miR‐224 levels were correlated with shorter survivalin osteosarcoma patients. Furthermore, overexpression of miR‐224 suppressed osteosarcoma cell proliferation, migration and invasion and contributed to the increased sensitivity of MG‐63 cells to cisplatin. We identified Rac1 as a direct target gene of miR‐224 in osteosarcoma. Rac1 expression was up‐regulated in the osteosarcoma cell lines and tissues, and there was an inverse correlation between Rac1 and miR‐224 expression in osteosarcoma tissues. Furthermore, rescuing Rac1 expression decreased the sensitivity of miR‐224‐overexpressing MG‐63 cells to cisplatin. We also demonstrated that ectopic expression of Rac1 promoted the proliferation, migration and invasion of miR‐224‐overexpressing MG‐63 cells. These data suggest that miR‐224 plays a tumour suppressor role in the development of osteosarcoma and is related to the sensitivity of osteosarcoma to cisplatin.
Highlights
Osteosarcoma is the most frequent primary bone tumour that arises from osteoid tissues in young adults and children [1,2,3,4]
The Rac1 vector promoted the expression of Rac1 in MG-63 cells In this study, we demonstrated that miR-224 was down-regulated in (Fig. 6A and B)
We observed that overexpression of miR-224 suppressed osteosarcoma cell proliferation, migration and invasion and contributed to the increased sensitivity of MG-63 cells to cisplatin
Summary
Osteosarcoma is the most frequent primary bone tumour that arises from osteoid tissues in young adults and children [1,2,3,4]. Recent evidence has demonstrated that miRNAs play critical roles in many biological processes, such as lineage determination and cell proliferation, migration, apoptosis and differentiation [2, 17,18,19]. MiR-224 is a well-known miRNA that plays important roles in the development of multiple tumours [28,29,30,31,32]. MiR-224 overexpression increased colorectal cancer cell proliferation by targeting PHLPP1 and PHLPP2 expression [33]. We determined that miR-224 expression was down-regulated in osteosarcoma cell lines and tissues and that lower miR-224 levels were correlated with shorter patient survival. We observed that overexpressing miR-224 suppressed osteosarcoma cell proliferation, migration and invasion.
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