Dataset Information

MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1? protein.

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-1? 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-1? axis may represent a potential therapeutic strategy to eradicate OS cells.

SUBMITTER: Zhang H

PROVIDER: S-EPMC5356804 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1α protein.

Zhang Heng H Guo Xiaofeng X Feng Xing X Wang Tingting T Hu Zhaohua Z Que Xiangyong X Tian Qingsong Q Zhu Tianbo T Guo Guixian G Huang Wei W Li Xinzhi X

Oncotarget 20170101 2

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, compare ...[more]

PMID: 27911265

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Project description:Background Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. Methods Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. Results Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. Conclusion Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria. Supplementary Information The online version contains supplementary material available at 10.1186/s10020-022-00525-1.

Dataset Information

MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1? protein.

Publications

MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1α protein.

Similar Datasets

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