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28 June 2019 : Clinical Research  

MicroRNA-181c Suppresses the Biological Progression of Osteosarcoma via Targeting SMAD7 and Regulating Transforming Growth Factor-β (TGF-β) Signaling Pathway

Youwei Fu1ABDF, Yin Tang1BCE, Junjie Wang1ACE, Zonghui Guo1ADFG*

DOI: 10.12659/MSM.916939

Med Sci Monit 2019; 25:4801-4810

Abstract

BACKGROUND: Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Increasing evidence suggests that dysfunction of microRNAs (miRNAs) plays a pivotal role in malignancies. The aim of this study was to evaluate the potential functions of miR-181c and verifying its regulatory effects on SMAD7 in osteosarcoma.

MATERIAL AND METHODS: The expressions of miR-181c and SMAD7 in osteosarcoma were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, invasion and migration abilities were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Transwell assay. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-181c and SMAD7. Western blot was performed to determine the functions of miR-181c on osteosarcoma cell epithelial-to-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling pathway.

RESULTS: Decreased expression levels of miR-181c and SMAD7 were identified in osteosarcoma using qRT-PCR. The downregulated miR-181c and SMAD7 expressions indicated poor prognosis of osteosarcoma patients. Moreover, miR-181c overexpression prominently repressed osteosarcoma cell proliferation, invasion, and migration abilities via modulating EMT and TGF-β signaling pathway. SMAD7 functioned as an important target for miR-181c in osteosarcoma cells. Furthermore, upregulation of miR-181c dramatically suppressed osteosarcoma tumorigenesis in vivo.

CONCLUSIONS: These findings indicated that miR-181c suppressed osteosarcoma progression, providing new insight into the pathogenesis and representing a potential therapeutic target for osteosarcoma.

Keywords: Epithelial-mesenchymal transition, Osteosarcoma, Smad7 Protein, Aged, Aged, 80 and over, Bone Neoplasms, Cell Movement, Cell Proliferation, Disease Progression, MicroRNAs, Middle Aged, Neoplasm Invasiveness, Signal Transduction, Transforming Growth Factor beta, Up-Regulation

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750