Abstract
Osteosarcoma (OS) is recognized as a common malignant tumor with a high trend of metastasis and diffusion. Despite the progresses that have been made in surgery, chemotherapy, and radiotherapy in the recent decades, the prognosis of patients with OS still remains poor. MiRNAs are being increasingly considered as new therapeutic targets for OS treatment. Our research aims to investigate the regulatory impact of miR-92a in the development of OS. Quantitative real-time PCR (qRT-PCR) results revealed that the expression of miR-92a was aberrantly overexpressed in human OS cell lines. By using cell counting kit-8 (CCK-8) assays, colony formation assays, flow cytometric analyses and Transwell assays, our data suggested that up-regulation of miR-92a promoted the proliferation, migration, and invasion of MNNG and U2OS cells, while inhibiting their apoptosis. In contrast, the knockdown of miR-92a effectively reversed these cellular biological behaviors. Furthermore, bioinformatics analysis indicated that Dickkopf-related protein 3 (DKK3) was a possible target of miR-92a. Subsequently, negative regulation of miR-92a on DKK3 was observed, which further supported the direct binding between them. In addition, silencing DKK3 rescued the inhibitory effect of miR-92a inhibitor on the development of OS. To sum up, our study revealed that miR-92a played a carcinogenic role in the growth of OS by promoting the tumorigenesis of OS cells via targeting of DKK3, thus revealing a new therapeutic target for OS.
Highlights
Osteosarcoma (OS) is the most common primary bone malignant tumor, predominantly occurring in children and adolescents [3]
At the beginning of the experiment, we analyzed the data in GSE28423 from the NCBI-Gene Expression Omnibus (GEO) database, which contained 19 OS cell lines and four normal bones [21]
After transfection for 48 h, Quantitative real-time PCR (qRT-PCR) analysis showed that the transcription levels of miR-92a in both MNNG and U2OS cells were remarkably increased in the mimics group, while those in the inhibitor group were obviously decreased
Summary
Osteosarcoma (OS) is the most common primary bone malignant tumor, predominantly occurring in children and adolescents [3]. It is characterized by high malignancy and metastatic potency, accounting for nearly 50% of metastatic bone sarcomas [11,19]. A combination of surgical resection, chemotherapy, and radiotherapy is the main treatment for OS, and has led to considerable progress in the development of therapeutic strategies for OS [31,25]. Distant metastasis and local recurrence can still occur in a considerable number of patients, whose prognosis is extremely poor. We urgently need to clarify the molecular mechanism of the occurrence, development, and metastasis of OS
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