SKP2, positively regulated by circ_ODC1/miR-422a axis, promotes the proliferation of retinoblastoma.

Abstract

Retinoblastoma (RB) is the most common intraocular malignancy in infants and children. S-phase kinase-associated protein 2 (SKP2) has been unmasked as an oncogene in a great many of carcinomas. The biologic function and the detailed molecular mechanism of SKP2 in RB need to be better understood. In this study, real-time quantitative polymerase chain reaction and Western blot showed the ectopic expression of SKP2 in RB tissues and cell lines. Loss of function assays showed the attenuated cell proliferation in RB as a result of SKP2 knockdown. In addition, bioinformatics analysis predicted the interaction between SKP2 and miR-422a. Luciferase reporter assay and Pearson's correlation analysis validated the negative correlation between miR-422a and SKP2. MiR-422a overexpression led to a decline of SKP2 expression and cell growth in RB. The binding capacity between miR-422a and circ_ODC1 was also predicted by bioinformatics analysis. Pearson's correlation analysis and luciferase reporter assay confirmed that circ_ODC1 is negatively correlated with miR-422a. Silencing circ_ODC1 resulted in a rise in miR-422a expression and RB cell growth. Moreover, reduced cell growth was restored by SKP2 overexpression. In a word, SKP2, induced by circ_ODC1 and miR-422a, promotes RB proliferation. Our new findings in this research might expedite the discovery of novel prognostic markers and therapeutic targets of RB.

• Authors: Shanshan Du, Shuai Wang, Fengyan Zhang, Yong Lv
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 121 Issue 1 Pg. 322-331 (01 2020) ISSN: 1097-4644 [Electronic] United States
• PMID: 31297892 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Dicarboxylic Acid Transporters
• MIRN422 microRNA, human
• MicroRNAs
• Mitochondrial Membrane Transport Proteins
• RB1 protein, human
• RNA, Circular
• Retinoblastoma Binding Proteins
• S-Phase Kinase-Associated Proteins
• SKP2 protein, human
• SLC25A21 protein, human
• Ubiquitin-Protein Ligases

Topics

• Algorithms
• Animals
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Cell Proliferation
• Computational Biology
• Cytoplasm (metabolism)
• Dicarboxylic Acid Transporters (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Neoplasm Transplantation
• Promoter Regions, Genetic
• Protein Binding
• RNA, Circular (metabolism)
• Retinal Neoplasms (metabolism, pathology)
• Retinoblastoma (metabolism, pathology)
• Retinoblastoma Binding Proteins (metabolism)
• S-Phase Kinase-Associated Proteins (metabolism)
• Transfection
• Ubiquitin-Protein Ligases (metabolism)
• Up-Regulation