MiR-217 regulated autophagy through OPG/RANKL/RANK in giant cell tumor

Abstract

Aims Increasing evidences have suggested that microRNAs (miRNAs) play crucial roles in cancer development and progression. Our previous study showed that the level of miR-217 was remarkably lower in GCT cells and tissues, and the re-expression of miR-217 induced an inhibitory effect on occurrence and development of GCT in vitro. However, the mechanisms underlying the proliferation inhibition effect of miR-217 in GCT cells still remain unknown. Thus, this article is aimed to explore the mechanisms underlying the proliferation inhibition effect of miR-217 in GCT cells. Methods The GCT cells proliferative potential was measured by use of the MTT assay and BrdU straining. The changes in migration and invasion of GCT cells was determined by transwell assay. Finally, western blot and RT-PCR assays were employed to evaluate the expression of OPG/RANKL/RANK signaling pathway related-proteins. Result In the present study, the excessive upregulation of miR-217 markedly suppressed GCT cell proliferation and tumorigenesis in vitro and in vivo. Meanwhile, the overexpression of miR-217 could inhibit OPG/RANKL/RANK signal pathway in vitro and in vivo. Furthermore, the ALP activity was also significantly decreased in GCT cells by miR-217 treatment. Importantly, miR-217 could inhibit autophagy-related protein expression and autophagosomes/autolysosomes formation in GCT cells and tissues. Conclusion These results suggest that the upregulation of miR-217 inhibit the occurrence and development of GCT through inhibiting autophagy. This study also offers an effective therapeutic target to improve the survival rates of patients with CGT in the future.