Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1

Osteosarcoma is a common primary bone cancer that there are currently no effective treatment strategies for. Forkhead box M1 (FoxM1) is key in the development of osteosarcoma, and microRNA (miR)-216b serves an antitumor role by targeting FoxM1. Moreover, thiostrepton (TST), a natural thiazole antibi...

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Veröffentlicht in:Oncology letters 2020-12, Vol.20 (6), p.1-1
Hauptverfasser: Cai, Xiaobing, Xiao, Wenyu, Shen, Juexin, Lian, Hui, Lu, Yi, Liu, Xianmiao, Gu, Jisheng
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container_end_page 1
container_issue 6
container_start_page 1
container_title Oncology letters
container_volume 20
creator Cai, Xiaobing
Xiao, Wenyu
Shen, Juexin
Lian, Hui
Lu, Yi
Liu, Xianmiao
Gu, Jisheng
description Osteosarcoma is a common primary bone cancer that there are currently no effective treatment strategies for. Forkhead box M1 (FoxM1) is key in the development of osteosarcoma, and microRNA (miR)-216b serves an antitumor role by targeting FoxM1. Moreover, thiostrepton (TST), a natural thiazole antibiotic, induces antitumor effects and specifically targets FoxM1. Therefore, the present study investigated whether thiostrepton and miR-216b synergistically inhibited osteosarcoma cells by targeting FoxM1. The MTT assay, reverse transcription-quantitative PCR, a dual-luciferase reporter assay and flow cytometry were performed. Compared with the human osteoblast cell line hFOB1.19, miR-216b expression was significantly downregulated in the osteosarcoma cell lines U2OS, MG63 and Saos-2. By contrast, FoxM1 expression was significantly upregulated in osteosarcoma cell lines compared with the hFOB1.19 cell line. The results indicated that miR-216b targeted the 3′-untranslated region of FoxM1. Moreover, the results suggested that miR-216b cooperated with TST to decrease cell cytotoxicity and increase cell apoptosis. In addition, miR-216b cooperated with TST to increase Bax expression and decrease Bcl-2 expression. In conclusion, the combination of TST and miR-216b synergistically promoted osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1. Therefore, the present study suggested that the combination of TST and miR-216b may serve as a promising therapeutic strategy for osteosarcoma.
doi_str_mv 10.3892/ol.2020.12254
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Forkhead box M1 (FoxM1) is key in the development of osteosarcoma, and microRNA (miR)-216b serves an antitumor role by targeting FoxM1. Moreover, thiostrepton (TST), a natural thiazole antibiotic, induces antitumor effects and specifically targets FoxM1. Therefore, the present study investigated whether thiostrepton and miR-216b synergistically inhibited osteosarcoma cells by targeting FoxM1. The MTT assay, reverse transcription-quantitative PCR, a dual-luciferase reporter assay and flow cytometry were performed. Compared with the human osteoblast cell line hFOB1.19, miR-216b expression was significantly downregulated in the osteosarcoma cell lines U2OS, MG63 and Saos-2. By contrast, FoxM1 expression was significantly upregulated in osteosarcoma cell lines compared with the hFOB1.19 cell line. The results indicated that miR-216b targeted the 3′-untranslated region of FoxM1. Moreover, the results suggested that miR-216b cooperated with TST to decrease cell cytotoxicity and increase cell apoptosis. In addition, miR-216b cooperated with TST to increase Bax expression and decrease Bcl-2 expression. In conclusion, the combination of TST and miR-216b synergistically promoted osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1. 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subjects Apoptosis
Binding sites
Biotechnology
Bone cancer
Breast cancer
Cervical cancer
Cytotoxicity
Ewings sarcoma
Experiments
Laboratories
MicroRNAs
Oncology
Protein expression
Proteins
Sarcoma
Software
title Thiostrepton and miR‑216b synergistically promote osteosarcoma cell cytotoxicity and apoptosis by targeting FoxM1
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