MicroRNA-26a inhibits osteosarcoma cell proliferation by targeting IGF-1.

Xinyu Tan,Shicai Fan,Wen Wu,Yin Zhang

doi:10.1038/boneres.2015.33

Abstract

There are still controversies about the roles of microRNA-26a (miR-26a) in human malignancies, as it is a tumor suppressor in breast cancer, gastric cancer, and hepatocellular carcinoma, but is an oncogene in glioma and cholangiocarcinoma. Until now, the function of miR-26a in osteosarcoma remains largely elusive. Here, we found that miR-26a was downregualted in osteosarcoma tissues. Using in vitro and in vivo assays, we confirmed that miR-26a could inhibit the abilities of in vitro proliferation and suppress in vivo tumor growth in mouse model. Furthermore, we identified insulin-like growth factor 1 (IGF-1) as a novel and direct target of miR-26a and revealed that miR-26a exerted its tumor-suppressor function, at least in part, by inhibiting IGF-1 expression. These findings contribute to our understanding of the functions of miR-26a in osteosarcoma.

Highlights

Osteosarcoma is the most common primary malignancy, and it arises primarily in the metaphysis of the long bones in adolescents and young adults.[1,2] It leads to many deaths because of its rapid proliferation and metastasis.[3]
MiR-26a suppresses osteosarcoma cell proliferation To evaluate the biological significance of miR-26a in the development of osteosarcoma, we transfected with miR26a mimic or inhibitor into MG-63 and U2OS cells (Figure 2a), and examined cell proliferation using direct cell counting and MTS assays
Using in vitro and in vivo assays, we identify the tumor suppressor function of miR-26a in osteosarcoma

Summary

Introduction

Osteosarcoma is the most common primary malignancy, and it arises primarily in the metaphysis of the long bones in adolescents and young adults.[1,2] It leads to many deaths because of its rapid proliferation and metastasis.[3]. MiRNAs negatively regulate the expression of target messenger RNAs (mRNAs) by suppressing translation or decreasing the stability of mRNAs.[5] It has been found that miRNAs play crucial roles in various biological processes, including development, differentiation, apoptosis, and cell proliferation.[6] An increasing number of studies have demonstrated that miRNAs can function as oncogenes or tumor suppressors, and they are often dysregulated in tumors.[7,8,9,10]. There are still controversies about the roles of miR-26a in human malignancies, as it is a tumor suppressor in breast cancer,[11] gastric cancer,[12] and hepatocellular carcinoma,[13,14] but is an oncogene in glioma[14] and cholangiocarcinoma.[15] miR-26a was found to be downregulated in osteosarcoma previously,[16] its biological function and precise mechanism in osteosarcoma remain largely elusive

Methods

Results

Conclusion