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Published on: January 16, 2026
MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing
Heng Zhang1, Xiaofeng Guo2, Xing Feng3
1Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
Abstract:
Osteosarcoma (OS) is the most common primary bone tumor, occurring frequently in adolescents and possessing a high malignant severity. MicroRNAs play critical roles during OS development. Thus, elucidation of the involvement of specific microRNAs in the development of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-543 were significantly increased whereas the levels of PRMT9 were significantly decreased, compared to the paired normal bone tissue. Moreover, miR-543 and PRMT9 inversely correlated in the OS cell lines. Bioinformatics analyses predicted that miR-543 may target the 3'-UTR of PRMT9 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. MiR-543 promoted OS cell proliferation in vitro and in vivo. Mechanistically, miR-543 inhibited PRMT9-enhanced cell oxidative phosphorylation, while miR-543 depletion promoted PRMT9-increased HIF-1α instability and inhibited glycolysis in OS cells. Clinically, miR-543 expression was negatively correlated with PRMT9 expression in OS tissues. Together, our data provide important evidence for glycolysis in OS development, and suggest that targeting glycolytic pathway through miR-543/PRMT9/HIF-1α axis may represent a potential therapeutic strategy to eradicate OS cells.
Insights
MicroRNA-543 (miR-543) promotes osteosarcoma (OS) growth by inhibiting PRMT9, affecting cell metabolism. Targeting the miR-543/PRMT9/HIF-1α axis offers a potential therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a prevalent and aggressive bone cancer, particularly in adolescents.
- MicroRNAs are crucial regulators in cancer development, presenting potential therapeutic targets.
Purpose of the Study:
- To investigate the role of miR-543 in osteosarcoma (OS) development.
- To explore the relationship between miR-543 and PRMT9 in OS.
- To elucidate the therapeutic potential of targeting the miR-543/PRMT9 axis in OS.
Main Methods:
- Analysis of miR-543 and PRMT9 expression in OS tissues and cell lines.
- Bioinformatics prediction and luciferase-reporter assay to confirm miR-543 targeting of PRMT9.
- In vitro and in vivo experiments to assess the impact of miR-543 on OS cell proliferation.
- Investigation of the effects of miR-543 and PRMT9 on cellular oxidative phosphorylation, glycolysis, and HIF-1α stability.
Main Results:
- miR-543 levels were elevated, while PRMT9 levels were decreased in OS tissues.
- miR-543 directly targets and inhibits PRMT9 expression in OS cells.
- miR-543 promotes OS cell proliferation both in vitro and in vivo.
- miR-543 dysregulates cellular metabolism by inhibiting oxidative phosphorylation and affecting glycolysis and HIF-1α stability.
Conclusions:
- The miR-543/PRMT9/HIF-1α axis plays a significant role in osteosarcoma development.
- Targeting the glycolytic pathway via the miR-543/PRMT9/HIF-1α axis presents a promising therapeutic strategy for osteosarcoma.
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