title: MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1α 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-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.
authors.affiliation: Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Molecular Pharmacology, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|National Clinical Research Center of Digestive Diseases, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Que
authors.affiliation: Department of Medicine, Medical College, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Medicine, Medical College, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Tianbo
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Medicine, The Second Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Guixian
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics*; D002648:Child; D044783:F-Box Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D044783:F-Box Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C577592:MIRN543 microRNA, human; D035683:MicroRNAs; C457579:FBXO11 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: HIF-1α; PRMT9; glycolysis; miRNA-543; osteosarcoma