MicroRNA-488 inhibits proliferation, invasion and EMT in osteosarcoma cell lines by targeting aquaporin 3.

Yongzhi Zhang,Hu Chen,Zhi Guo,Jing Qiu

doi:10.3892/ijo.2018.4483

Abstract

It has been reported that aquaporin 3 (AQP3) expression is associated with the progression of numerous types of cancer and microRNA (miRNA/miR) processing. However, the effects and precise mechanisms of AQP3 in osteosarcoma (OS) have not been fully elucidated. The present study aimed to investigate the interaction between AQP3 and miR-488 in OS. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was performed to detect the levels of AQP3 and miR-488 in OS tissues and cell lines, respectively. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were detected to analyze the biological functions of miR-488 and AQP3 in OS cells. Furthermore, mRNA and protein levels of AQP3 was measured by RT-qPCR and western blot analysis. Furthermore, AQP3 was validated as an miR-488 target using luciferase assays in OS cells. The present study revealed that the miR-488 level was significantly downregulated in OS tissues and cell lines, and that the expression of AQP3 was markedly increased. Notable, the low miR-488 expression level was associated with upregulated AQP3 expression in OS tissues. Furthermore, introduction of miR-488 markedly suppressed the proliferation, invasion and EMT of OS cells. However, miR-488-knockdown increased the proliferation, invasion and EMT of OS cells. The present study demonstrated that miR-488 could directly target AQP3 using bioinformatics analysis and luciferase reporter assays. In addition, AQP3-silencing had similar effects to miR-488 overexpression on OS cells. Overexpression of AQP3 in OS cells partially reversed the inhibitory effects of miR-488 mimic. miR-488 inhibited the proliferation, invasion and EMT of OS cells by directly downregulating AQP3 expression, and miR-488 targeting AQP3 was responsible for inhibition of the proliferation, invasion and EMT of OS cells.

Highlights

Osteosarcoma (OS) is the most common malignancy of bone and mainly arises in the metaphysis of the long bones in adolescents and young adults, accounting for 5% of all pediatric tumors and 8.9% of cancer-related mortalities in children [1,2]
The data indicated that the messenger RNAs (mRNAs) expression of aquaporin 3 (AQP3) was higher than that of other AQPs in OS tissues compared with the adjacent non-cancerous tissues (Fig. 1A)
The results of the present study demonstrated that miR‐488 suppressed the cell proliferation, invasion and epithelial-mesenchymal transition (EMT) of OS cells by directly decreasing AQP3 expression, and the targeting of AQP3 by miR‐488 was responsible for inhibiting the proliferation, invasion and EMT of OS cells (Fig. 9)

Summary

Introduction

Osteosarcoma (OS) is the most common malignancy of bone and mainly arises in the metaphysis of the long bones in adolescents and young adults, accounting for 5% of all pediatric tumors and 8.9% of cancer-related mortalities in children [1,2]. High malignancy, frequent relapse and metastasis are characteristics of OS. It has been reported that >50% of patients with OS are diagnosed as suffering metastasis, leading to a low cure rate and a low 5-year survival rate [3]. The 5-year survival rate has risen to 60-70% due to the development of comprehensive therapies [4]. Once patients develop recurrent or metastatic OS, the clinical prognosis remains poor. The precise molecular mechanisms of the development and progression of OS remain unclear. It is essential to investigate the pathogenesis and mechanisms of OS, which will contribute toward the development of strategies for the diagnosis, treatment and prognostic prediction of OS

Methods

Results

Conclusion