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Published on: March 15, 2018
MiR-217 regulates autophagy through OPG/RANKL/RANK in giant cell tumors
Chenyang Meng1, Boyong Jiang1, Wanlin Liu1
1The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010030, China.
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.
Insights
MicroRNA-217 (miR-217) upregulation suppresses germ cell tumor (GCT) growth by inhibiting autophagy. This discovery provides a potential therapeutic target for improving GCT patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are implicated in cancer development.
- Lower miR-217 levels were observed in germ cell tumor (GCT) cells and tissues.
- Previous studies indicated miR-217 re-expression inhibits GCT occurrence and development in vitro, but mechanisms were unclear.
Purpose of the Study:
- To investigate the mechanisms by which miR-217 inhibits proliferation in GCT cells.
- To explore the role of miR-217 in regulating GCT cell behavior and signaling pathways.
Main Methods:
- Assessed GCT cell proliferation using MTT assay and BrdU staining.
- Evaluated GCT cell migration and invasion via transwell assays.
- Analyzed OPG/RANKL/RANK signaling pathway and autophagy-related protein expression using Western blot and RT-PCR.
Main Results:
- miR-217 overexpression significantly suppressed GCT cell proliferation and tumorigenesis in vitro and in vivo.
- miR-217 inhibited the OPG/RANKL/RANK signaling pathway and decreased ALP activity.
- miR-217 suppressed autophagy-related protein expression and autophagosome/autolysosome formation in GCT cells and tissues.
Conclusions:
- miR-217 upregulation inhibits GCT development by blocking autophagy.
- Targeting miR-217 represents a potential therapeutic strategy for GCT patients.
- This study offers insights into the molecular mechanisms of GCT progression and potential treatment avenues.
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