ABSTRACT
BACKGROUND: Increasing evidence suggests that microRNAs (miRNAs) play a crucial role in cancer development and progression. Our previous study showed remarkably lower levels of miR-217 in GCT cells and tissues, and miR-217 re-expression inhibited the occurrence and development of GCT in vitro; however, the associated mechanisms remain unknown. Thus, this study aimed to explore the mechanisms underlying the proliferation inhibitory effect of miR-217 in GCT cells. METHODS: The proliferative potential of the GCT cells was measured with an MTT assay and BrdU straining. Changes in GCT cell migration and invasion was assessed by a transwell assay. Finally, Western blot and RT-PCR assays were employed to evaluate OPG/RANKL/RANK signaling pathway-related protein expression. RESULTS: The excessive upregulation of miR-217 markedly suppressed GCT cell proliferation and tumorigenesis both in vitro and in vivo. miR-217 overexpression could inhibit the OPG/RANKL/RANK signaling pathway in vitro and in vivo. Furthermore, ALP activity was significantly decreased in GCT cells following miR-217 treatment. Importantly, miR-217 could inhibit autophagy-related protein expression and autophagosome/autolysosome formation in GCT cells and tissues. CONCLUSION: These results suggest that miR-217 upregulation could inhibit the occurrence and development of GCT by blocking autophagy. These findings offer an effective therapeutic target to improve the survival rates of patients with CGT in the future.
Subject(s)
Giant Cell Tumors , MicroRNAs , Humans , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , MicroRNAs/metabolism , Signal Transduction/genetics , Autophagy/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Cell Line, Tumor , RANK Ligand/metabolismABSTRACT
Dynamic balance of bone metabolism is one of the important factors to maintain normal osseous tissue function. When the balance is broken, it causes bone damage and even bone metabolic disease. However, the mechanism of bone metabolism is still unclear, the signal pathway is complex, and the treatment of diseases is still under study. The research on the mechanism of bone metabolism by Chinese materia medica has become a new direction in the treatment of bone metabolism diseases. At present, common mechanisms in bone metabolism include OPG/RANKL/RANK signal pathway, Wnt/β-catenin signal pathway, TGF-β/BMP/Smad signal pathway, and NF-κB signal pathway. In this paper, the research on the above pathways was reviewed, so as to provide a reference for further exploring the treatment of bone metabolism diseases with Chinese materia medica.
