Abstract
This study aimed to explore the roles and relationship between FUsed in Sarcoma (FUS)-C/EBP HOmologous Protein (CHOP), microRNA (miR)-486 and cyclin dependent kinase 4 (CDK4) in myxoid liposarcoma, and determined whether FUS-CHOP can regulate proliferation and apoptosis of myxoid liposarcoma cells by regulating miR-486/CDK4 axis. The levels of miR-486, CDK4 and FUS-CHOP in myxoid liposarcoma samples/adjacent normal muscle tissues and myxoid liposarcoma/human adipose-derived stem cell line were evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation and apoptosis were performed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and flow cytometry, respectively. Furthermore, the apoptosis-related proteins were determined using Western blot assay. We found that miR-486 was down-regulated, FUS-CHOP and CDK4 were up-regulated in myxoid liposarcoma tissues and myxoid liposarcoma cell lines. Moreover, FUS-CHOP-siRNA distinctly suppressed FUS-CHOP level and increased miR-486 levels in 1955/91 cells. Our results demonstrated that knockdown of FUS-CHOP by siRNA inhibited 1955/91 growth, promoted cell apoptosis and enhanced cleaved Caspase3 protein expression. However, all these data were reversed by miR-486 inhibitor. Similarly, compared to mimic control, miR-486 mimic markedly reduced 1955/91 cells growth, induced cell apoptosis and fortified cleaved Caspase3 level, while these results were abolished by CDK4-plasmid. Collectively, our observations clearly suggested that FUS-CHOP regulated myxoid liposarcoma cell proliferation and apoptosis by the regulation of miR-486/CDK4 axis, indicating the potential use of FUS-CHOP-siRNA as a promising therapy for myxoid liposarcoma.
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This study was supported by Zhejiang Medical and Health Science and Technology Plan Project (Grant Nos. 2017KY249, 2019KY332).
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Wu, H., Xia, L. & Xu, H. Role of FUS-CHOP in Myxoid Liposarcoma via miR-486/CDK4 Axis. Biochem Genet 60, 1095–1106 (2022). https://doi.org/10.1007/s10528-021-10151-x
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DOI: https://doi.org/10.1007/s10528-021-10151-x