Abstract
BackgroundThis study aims to investigate the role of microRNA-92a (miR-92a) in metastasis of osteosarcoma (OS) cells in vivo and in vitro by regulatingTCF21 with the transmission of bone marrow derived mesenchymal stem cells (BMSCs).MethodsBMSCs were isolated, purified and cultured from healthy adult bone marrow tissues. The successfully identified BMSCs were co-cultured with OS cells, and the effects of BMSCs on the growth metastasis of OS cells in vitro and in vivo were determined. qRT-PCR and western blot analysis was used to detect the expression of miR-92a and TCF21 in OS cells and OS cells co-cultured with BMSCs. Proliferation, invasion and migration of OS cells transfected with miR-92a mimics and miR-92a inhibitors was determined, and the tumorigenesis and metastasis of OS cells in nude mice were observed. Expression of miR-92a and TCF21 mRNA in tissue specimens as well as the relationship between the expression of miR-92a and the clinicopathological features of OS was analyzed.ResultsBMSCs promoted proliferation, invasion and migration of OS cells in vitro together with promoted the growth and metastasis of OS cells in vivo. Besides, high expression of miR-92a was found in OS cells co-cultured with BMSCs. Meanwhile, overexpression of miR-92a promoted proliferation, invasion and migration of OS cells in vitro as well as promoted growth and metastasis of OS cells in vivo. The expression of miR-92a increased significantly, and the expression of TCF21 mRNA and protein decreased significantly in OS tissues. Expression of miR-92a was related to Ennecking staging and distant metastasis in OS patients.ConclusionCollectively, this study demonstrates that the expression of miR-92a is high in OS and BMSCs transfers miR-92a to inhibit TCF21 and promotes growth and metastasis of OS in vitro and in vivo.
Highlights
This study aims to investigate the role of microRNA-92a in metastasis of osteosarcoma (OS) cells in vivo and in vitro by regulatingTCF21 with the transmission of bone marrow derived mesenchymal stem cells (BMSCs)
After osteogenic induction of human BMSCs, a large number of red staining of calcium nodules could be seen under a microscope by alizarin red staining, which showed that the cells had good osteogenic differentiation function (Fig. 1c)
The results indicated that human BMSCs was isolated and cultured successfully
Summary
This study aims to investigate the role of microRNA-92a (miR-92a) in metastasis of osteosarcoma (OS) cells in vivo and in vitro by regulatingTCF21 with the transmission of bone marrow derived mesenchymal stem cells (BMSCs). Osteosarcoma (OS), is the most commonly occurring primary malignant bone tumor, which mainly affects the metaphysis of long bones amongst children and adolescents [1]. OS comprises approximately 2.4% of all malignancies in pediatric patients, and about 20% of all primary bone cancers [1, 2]. Despite many tumors respond to chemotherapy initially, OS patients with relapsed disease and metastatic disease continue to show extremely poor survival outcomes [4, 5]. Bone marrowderived mesenchymal stem cells (BMSCs) are described as locally adjacent to the tumor tissues, which might directly interact with tumor cells [6]. It has been reported that the expression and function of specific microRNA (miRNA) in OS will potentially result in the identification of new biomarkers and therapeutic targets in OS
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