Role of FUS-CHOP in Myxoid Liposarcoma via miR-486/CDK4 Axis

• Published in: Biochemical genetics Vol. 60; no. 3; pp. 1095 - 1106
• Main Authors: Wu, Hao, Xia, Liming, Xu, Haichao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2022; Springer Nature B.V
• Subjects: Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; CCAAT/enhancer-binding protein; Cell growth; Cell proliferation; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - genetics; Cyclin-Dependent Kinase 4 - metabolism; Flow cytometry; FUS protein; Homology; Human Genetics; Humans; Kinases; Liposarcoma; Liposarcoma, Myxoid - genetics; Liposarcoma, Myxoid - metabolism; Medical Microbiology; MicroRNAs - genetics; miRNA; Muscles; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Original Article; Polymerase chain reaction; Proteins; Reverse transcription; Ribonucleic acid; RNA; RNA, Small Interfering - genetics; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - metabolism; Sarcoma; siRNA; Stem cells; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; Western blotting; Zoology; FUS-CHOP; Myxoid liposarcoma; miR-486/CDK4 axis; Apoptosis
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1007/s10528-021-10151-x

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.