Oncotarget

Research Papers:

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

Heng Zhang, Xiaofeng Guo, Xing Feng, Tingting Wang, Zhaohua Hu, Xiangyong Que, Qingsong Tian, Tianbo Zhu, Guixian Guo, Wei Huang and Xinzhi Li _

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Oncotarget. 2017; 8:2342-2355. https://doi.org/10.18632/oncotarget.13672

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Abstract

Heng Zhang1,*, Xiaofeng Guo7,*, Xing Feng2, Tingting Wang3,4,*, Zhaohua Hu1, Xiangyong Que1, Qingsong Tian5, Tianbo Zhu5, Guixian Guo6, Wei Huang1, Xinzhi Li1

1Department of Orthopedics, Renhe Hospital, China Three Gorges University, Yichang, Hubei, China

2Department of Molecular Pharmacology, Rutgers University, New Brunswick, New Jersey, USA

3Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China

4National Clinical Research Center of Digestive Diseases, Beijing, China

5Department of Medicine, Medical College, China Three Gorges University, Yichang, Hubei, China

6Department of Medicine, The Second Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China

7Medical College of Xiamen University, Xiamen, Fujian, China

*These authors contributed equally to this work

Correspondence to:

Xinzhi Li, email: [email protected]

Xing Feng, email: [email protected]

Keywords: osteosarcoma, miRNA-543, glycolysis, PRMT9, HIF-1α

Received: April 17, 2016     Accepted: November 06, 2016     Published: November 28, 2016

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.


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