miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma
| Autor: | Zhen Tian, Huan-Ye Zhu, Xun-Yan Ouyang, Gan Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Biology lcsh:RC254-282 miR-133b 03 medical and health sciences 0302 clinical medicine microRNA Genetics medicine Viability assay Ras/MAPK signaling lcsh:QH573-671 Protein kinase B PI3K/AKT/mTOR pathway Osteosarcoma lcsh:Cytology Fibroblast growth factor receptor 1 Tumor suppressor lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease stomatognathic diseases PI3K/Akt signaling 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Primary Research |
| Zdroj: | Cancer Cell International Cancer Cell International, Vol 18, Iss 1, Pp 1-12 (2018) |
| ISSN: | 1475-2867 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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