Circ_0002669 promotes osteosarcoma tumorigenesis through directly binding to MYCBP and sponging miR-889-3p

• Published in: Biology direct 2024-04, Vol.19 (1), p.25-25, Article 25
• Main Authors: Zhang, Ying, Zhan, Yizhou, Liu, Zhaoyong, Guo, Huancheng, Liu, Dongchen, Chen, Chuangzhen
• Format: Article
• Language: English
• Subjects: Analysis; Antibodies; Biotin; Bone cancer; Bone Neoplasms - genetics; c-Jun protein; c-Myc protein; Cancer; Carcinogenesis; Carcinogenesis - genetics; Care and treatment; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Circ_0002669; Circular RNA; Cytokinesis; Degradation; Diagnosis; DNA polymerase; DNA-Binding Proteins; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Glioma; Health aspects; Humans; Immunoprecipitation; Liver cancer; Malignancy; Mass spectroscopy; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; miR-889-3p; miRNA; Myc protein; MYCBP; Osteosarcoma; Osteosarcoma - genetics; Proliferation; Proteasomes; Proteins; Sarcoma; Spectroscopy; Survival; Thyroid gland; Transcription Factors; Tumorigenesis; Tumors; Ubiquitin; Ubiquitination; Vitamin B complex
• ISSN: 1745-6150; 1745-6150
• DOI: 10.1186/s13062-024-00466-1

Circular RNAs (circRNAs) are a class of highly multifunctional single-stranded RNAs that play crucial roles in cancer progression, including osteosarcoma (OS). Circ_0002669, generated from the dedicator of cytokinesis (DOCK) gene, was highly expressed in OS tissues, and negatively correlated with OS patient survival. Elevated circ_0002669 promoted OS cell growth and invasion in vivo and in vitro. By biotin pulldown and mass spectroscopy, we found that circ_0002669 directly bound to MYCBP, a positive regulator of c-myc, to prevent MYCBP from ubiquitin-mediated proteasome degradation. In addition, circ_0002669 interacted with miR-889-3p and served as a miRNA sponge to increase the expression of MYCBP, as determined by luciferase assays and RNA immunoprecipitation. Functional rescue experiments indicated MYCBP acted as a key factor for circ_0002669- and miR-889-3p-regulated OS cell proliferation and migration. Increased expression of c-myc-associated genes, such as CCND1, c-Jun and CDK4, were found in circ_0002669- and MYCBP-overexpressing OS cells. Our data thus provide evidence that circ_0002669 promotes OS malignancy by protecting MYCBP from protein ubiquitination and degradation and blocking miR-889-3p-mediated inhibition of MYCBP expression.