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miR-181d-5p-FOXP1 feedback loop modulates the progression of osteosarcoma.

Authors
  • Chen, Haojie1
  • Xiao, Zhenguang2
  • Yu, Ronghua1
  • Wang, Yi1
  • Xu, Ruijun1
  • Zhu, Xiaodong3
  • 1 Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 XianXia Road, Shanghai, 200336, China. , (China)
  • 2 Department of Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 XianXia Road, Shanghai, 200336, China. , (China)
  • 3 Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 XianXia Road, Shanghai, 200336, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Sep 10, 2018
Volume
503
Issue
3
Pages
1434–1441
Identifiers
DOI: 10.1016/j.bbrc.2018.07.060
PMID: 30031607
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

MicroRNAs (miRNAs) are playing more and more fundamental roles in the progress of human cancers. miR-181d-5p has not been fully elucidated in human cancers. In this study, we aimed to investigate the biological function and mechanism of miR-181d-5p in osteosarcoma (OS). At first, the expression conditions of miR-181d-5p were identified in OS tissues and cell lines. Downregulation of miR-181d-5p was identified to be a significant prognostic factor for patients with OS. Using the bioinformatics analysis, the putative target mRNA (FOXP1) of miR-181d-5p was found out. Similarly, the expression conditions and prognostic value of FOXP1 were identified in OS. To validate the tumor suppressive role of miR-181d-5p in OS, gain or loss of function assays were carried out in OS cell lines. The results indicated the anti-oncogenic function of miR-181d-5p in OS. Subsequently, the oncogenic function of FOXP1 in OS was identified by functional assays. Rescue assays manifested that the oncogenic function of FOXP1 can be partially reversed by miR-181d-5p. Combining with the result of luciferase reporter assay, we confirmed that miR-181d-5p can act as a tumor suppressor in OS via targeting FOXP1. Further mechanism experiments revealed that FOXP1 can suppressed the transcription activity of miR-181d-5p by acting as a transcription inhibitor. In conclusion, our study revealed that miR-181d-5p-FOXP1 feedback loop modulates cell proliferation and metastasis in osteosarcoma. Copyright © 2018. Published by Elsevier Inc.

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