MiR-218 promotes apoptosis of U2OS osteosarcoma cells through targeting BIRC5.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-218 promotes apoptosis of U2OS osteosarcoma cells through targeting BIRC5, by D.-Z. Wang, S.-F. Jing, S.-B. Hao, X.-Y. Huang, Q.-T. Miao, J.-F. Gao, published in Eur Rev Med Pharmacol Sci 2018; 22(20): 6650-6657-DOI: 10.26355/eurrev_201810_16140-PMID: 30402837" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16140.

MiR-218 promotes apoptosis of U2OS osteosarcoma cells through targeting BIRC5.

OBJECTIVE: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is a member of apoptosis inhibition family which suppresses caspase activity. Osteosarcoma tissues have significantly higher BIRC5 and lower microRNA-218 (miR-218) level than adjacent tissues, indicating tumor suppressor role of miR-218 in osteosarcoma. Bioinformatics analysis showed satisfactory targeting correlation between miR-218 and 3'-UTR of BIRC5 mRNA. This study, thus, investigated if dysregulation of miR-218 and BIRC5 affected apoptosis of osteosarcoma cells U2OS. PATIENTS AND METHODS: A total of 42 osteosarcoma patients were collected for tumor and adjacent tissues to compare miR-218 and BIRC5 expressions. Dual-luciferase reporter gene assay examined targeted regulation between miR-218 and BIRC5. In vitro cultured U2OS cells were treated with miR-218 mimic and/or si-BIRC5. Caspase-3 activity was measured by spectrometry while flow cytometry was used to test cell apoptosis, plus protein expression assay by Western blot assay. RESULTS: Compared to adjacent tissues, osteosarcoma tissues had significantly depressed miR-218 expression and elevated BIRC5 expression (p<0.05). miR-21 targeted 3'-UTR of BIRC5 to suppress its expression. The elevation of miR-218 and/or silencing BIRC5 significantly depressed BRIC5-induced inhibition on caspase-5, and facilitated U2OS cell apoptosis (p<0.05). CONCLUSIONS: We observed that miR-218 was significantly down-regulated in osteosarcoma tissues, which had elevated BIRC5 expression. MiR-218 targeted and inhibited BIRC5 expression, weakened caspase-5 inhibition by BIRC5, and facilitated U2OS osteosarcoma cell apoptosis.

Antitumor Effect of Docetaxel in Osteosarcoma by the Inhibition of Wnt Signal Channel.

Osteosarcoma (OS) is the most common type of malignant bone tumor in adults and children. Despite the great strides in biology and medicine, the survival rate of patients with metastatic disease remains very poor. This rate has been staggering with recurrence and metastasis. In the present study, we proposed Wnt/ß-catenin pathway as a key biological target for the effective treatment in OS. Wnt signaling has been reported to play important roles in osteoblastogenesis. We hypothesized that docetaxel (DTX) will effectively arrest the osteosarcoma progression by suppressing the Wnt/ß-catenin pathway in OS cells. Our results show that DTX significantly inhibited the cell proliferation of U2OS and SaOS-2 cancer cells in a time-dependent and dose-dependent manner. DTX inhibited the intrinsic transcriptional activity of ß-catenin/Tcf in U2OS cancer cells and SaOS-2 cancer cells. GSK-3ßinhibitor (SB216763) treatment remarkably increased the ß-catenin/Tcf transcriptional activities. The transcriptional activities have been increased by around ~200% due to the decrease in the degradation of ß-catenin mediated through GSK-3ß. Summarizing, present study clearly showed that DTX inhibited Wnt/ß-catenin signalling pathways and significantly reduced the matrix metallopeptodase 9 (MMP-9) protein expressions and its activity. Taken together, our findings provide novel insight on the effect of anticancer small molecules to improve the outcomes in osteosarcoma.