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

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

  • Biol Direct. 2024 Apr 3;19(1):25. doi: 10.1186/s13062-024-00466-1.
Ying Zhang # 1 2,  Yizhou Zhan # 3,  Zhaoyong Liu # 4,  Huancheng Guo 4,  Dongchen Liu 5,  Chuangzhen Chen 3
Affiliations

Affiliations

  • 1 Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, 515041, Shantou, Guangdong, PR China. yzhangmimazi@stu.edu.cn.
  • 2 Department of Clinical Research Center, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, 515041, Shantou, Guangdong, China. yzhangmimazi@stu.edu.cn.
  • 3 Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, 515041, Shantou, Guangdong, PR China.
  • 4 Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, No.57 Changping Road, 515041, Shantou, Guangdong, China.
  • 5 Department of Clinical Research Center, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, 515041, Shantou, Guangdong, China.
  • # Contributed equally.
PMID: 38570856 DOI: 10.1186/s13062-024-00466-1
Abstract

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.

Keywords

Circ_0002669; MYCBP; Osteosarcoma; miR-889-3p.

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