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

Abstract

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.

The expression of miRNA-216b is negatively correlated with 18F-FDG uptake in non-small cell lung cancer

“…miRNA 216b was also downregulated in pancreatic cancer tissue and appeared to be related with the inhibition of pancreatic cancer cells proliferation as well as a KRAS-silencing induced apoptosis [ 45 ]. In addition, miRNA-216b could suppress FoxM1 expression in human glioma, osteosarcoma, liver cancer, cervical cancer, melanoma, and NSCLC [ 46 – 51 ]. Some studies demonstrated that miRNA-216b can inhibit lung cancer cell growth via diverse signal pathways [ 6 , 47 , 52 , 53 ] and it was associated with cisplatin sensitivity by modulating autophagy [ 54 – 56 ] and prognosis [ 57 ].…”

Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis

“…miR-216b has an antitumor role by targeting FoxM1 in OS [96] and suppressing the migratory and invasive potential of cells. In addition, miR-216b expression synergistically inhibits cytotoxicity and stimulates apoptosis in OS cells by increasing Bax expression and decreasing Bcl-2 expression [96]. Low expression of miR-134 was observed in OS cell lines (U2OS, MG63).…”

The Role of Forkhead Box Family in Bone Metabolism and Diseases

“…FoxM1 is highly expressed in human OS tissues and cell lines, and downregulation of FoxM1 expression was found to inhibit the viability, migration, and invasive growth of OS cells (Zhu et al, 2020b). Recent studies have shown that avasimibe (Wang et al, 2019a), diallyl disulfide (Li et al, 2018), thiostrepton (Cai et al, 2020), and some miRNAs [including miR-134 (Li et al, 2018), miR-370 (Duan et al, 2015), miR-216b (Wang et al, 2019b), andmiR-197 (Sun et al, 2020)] inhibit the proliferation and invasive growth of OS cells by directly or indirectly downregulating FoxM1 expression.…”