Biochemical and Biophysical Research Communications
MiR-183 inhibits osteosarcoma cell growth and invasion by regulating LRP6-Wnt/β-catenin signaling pathway
Introduction
Osteosarcoma (OS), which is characterized by production of osteoid or immature bone, derives from mesenchymal cells and mostly originates from bone and rarely from soft tissues [1]. This neoplasm has a highly malignant tendency, which mainly occurs in children and adolescents with an incidence rate of approximately 4.4 per million [2]. The overall 5-year survival rate of OS has improved to approximately 70% because of advances in surgical and synthetic therapeutic methods [3]. However, 30% of patients diagnosed with OS will not survive for more than 5 years, because of its highly malignant tendency to rapidly destroy surrounding tissues and metastasize [4].
MicroRNAs (miRNAs) are small, non-coding, 19–25 nucleotide RNAs that regulate gene expression by binding to the 3′-untranslated region (UTR) of their target mRNA molecules to repress transcription or induce mRNA degradation [5,6]. It has been demonstrated that miRNAs are involved in various cellular processes such as cell proliferation, apoptosis, metastasis, and invasion [7,8]. Growing evidence suggests that deregulation of miRNAs may contribute to many types of human cancers including OS [[9], [10], [11], [12]]. Extensive research has shown that microRNA-183 (miR-183) deregulates and plays major roles in many tumors including colorectal cancer, melanoma, prostate cancer, breast cancer, and OS [9,[13], [14], [15], [16]]. However, the role of miR-183 in OS pathogenesis is still largely unknown.
In the present study, we first showed that miR-183 had a tumor-suppressive function in OS by suppressing OS cell growth, migration, and invasion. Then, we characterized low density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-183. MiR-183 interacted with the 3′-UTR of LRP6 to suppress the Wnt/β-catenin signaling pathway to mediate its tumor-suppressive effect on the proliferation and invasion of OS cells. These findings may be useful for the development of possible clinical approaches for OS treatment.
Section snippets
Cell lines and mice
OS cell lines SOSP-9607, MG63, U20S, Saos-2, and SV40, and immortalized human fetal osteoblastic cell line hFOB 1.19 were obtained from the American Type Culture Collection (Chicago, IL, USA) and grown in complete growth medium as recommended by the manufacturer. The cells were maintained in a humidified atmosphere with 5% CO2 at 37.1 °C. All cell lines were regularly authenticated by checking their morphology.
Female BALB/c mice (4–5 weeks old) and male BALB/c mice (5 weeks old) were obtained
MiR-183 expression patterns in OS cells
To examine the expression levels of miR-183 in OS cell lines SOSP-9607, MG63, U20S, and Saos-2, we employed qRT-PCR. The results showed that MG63 cells expressed the lowest level of miR-183 mRNA (p < 0.01) and U20S cells expressed the highest miR-183 level among the four OS cells compared with hFOB1.19 cells (p < 0.05) (Supplementary Fig. 1A). Next, MG63 cells were infected with miR-183 or control lentiviral vectors, and U20S cells were infected with miR183 inhibitor or control lentiviral
Discussion
OS is a tumor with rapid progression, a high metastatic potential, and poor clinical prognosis [21]. Because of the low survival rate of metastatic OS, it is urgent to develop novel and effective therapeutic strategies for OS. In the present study, we showed that miR-183 has a tumor-suppressive function in OS. To better understand the molecular mechanisms through which miR-183 suppressed the growth and metastasis of OS cells, we performed functional experiments. Our results demonstrated that
Conflicts of interest
The authors have no conflicts of interest to disclose.
Acknowledgments
None.
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