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Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary research

miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma

Authors: Gan Gao, Zhen Tian, Huan-Ye Zhu, Xun-Yan Ouyang

Published in: Cancer Cell International | Issue 1/2018

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Abstract

Background

Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. However, little is known on the biological and functional significance of miR-133b/FGFR1 regulation in osteosarcoma.

Methods

The expressions of miR-133b and FGFR1 were examined by RT-qPCR and compared between 30 paired normal bone tissues and OS tissues, and also between normal osteoblasts and three OS cells lines, MG-63, U2OS, and SAOS-2. Using U2OS and MG-63 as the model system, the functional significance of miR-133b and FGFR1 was assessed on cell viability, proliferation, apoptosis, migration/invasion, and epithelial–mesenchymal transition (EMT) by overexpressing miR-133b and down-regulating FGFR1 expression, respectively. Furthermore, the signaling cascades controlled by miR-133b/FGFR1 were examined.

Results

miR-133b was significantly down-regulated while FGFR1 robustly up-regulated in OS tissues and OS cell lines, when compared to normal bone tissues and normal osteoblasts, respectively. Low miR-133b expression and high FGFR1 expression were associated with location of the malignant lesion, advanced clinical stage, and distant metastasis. FGFR1 was a direct target of miR-133b. Overexpressing miRNA-133b or knocking down FGFR1 significantly reduced the viability, proliferation, migration/invasion, and EMT, but promoted apoptosis of both MG-63 and U2OS cells. Both the Ras/MAPK and PI3K/Akt intracellular signaling cascades were inhibited in response to overexpressing miRNA-133b or knocking down FGFR1 in OS cells.

Conclusion

miR-133b, by targeting FGFR1, presents a plethora of tumor suppressor activities in OS cells. Boosting miR-133b expression or reducing FGFR1 expression may benefit OS therapy.
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Metadata
Title
miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma
Authors
Gan Gao
Zhen Tian
Huan-Ye Zhu
Xun-Yan Ouyang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0696-7

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