Circular RNA circ_0001946 acts as a competing endogenous RNA to inhibit glioblastoma progression by modulating miR‐671‐5p and CDR1

• Published in: Journal of cellular physiology Vol. 234; no. 8; pp. 13807 - 13819
• Main Authors: Li, Xinxing, Diao, Hongyu
• Format: Journal Article
• Language: English
• Published: United States 01.08.2019
• Subjects: Animals; Autoantigens - genetics; Autoantigens - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - pathology; cerebellar degeneration‐related autoantigen 1 (CDR1); circ_0001946; Disease Progression; Gene Expression Regulation, Neoplastic - genetics; glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Heterografts; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐671‐5p; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; proliferation; RNA, Circular - genetics; RNA, Circular - metabolism; circ_0001946; glioblastoma; proliferation; miR-671-5p; cerebellar degeneration-related autoantigen 1 (CDR1)
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.28061

Objectives In many malignant tumors, circRNAs play an important role. However, the biological role and clinical significance of circRNAs remain unclear. In this study, we investigated the effects of circ_0001946 on the progression of glioblastoma (GBM) and the molecular mechanism of circ_0001946. Methods Microarrays were applied to test the expression profiles of circRNAs and messenger RNAs (mRNAs). Coexpressed genes were identified by constructing differentially expressed circRNA–mRNA networks. The expression of circ_0001946, miR‐671‐5p, and cerebellar degeneration‐related autoantigen 1 (CDR1) was detected by real‐time quantitative PCR, and the protein expression of CDR1 was determined by western blotting. A dual‐luciferase reporter assay was used to evaluate potential miR‐671‐5p target sites on circ_0001946 and CDR1. The proliferation, apoptosis, migration, and invasion of GBM cells were assessed by a colony formation assay, flow cytometry assay, transwell migration assay, and transwell invasion assay. Xenograft mouse models were used to determine the role of circ_0001946 in vivo. Results The expression of circ_0001946 and CDR1 was low and that of miR‐671‐5p was high in GBM cells. Circ_0001946 suppressed the expression of miR‐671‐5p, thus upregulating the expression of CDR1, the gene downstream of miR‐671‐5p. Circ_0001946 and CDR1 reduced proliferation, migration, and invasion and increased apoptosis in GBM cells, whereas miR‐671‐5p had an opposite effect. The xenograft mouse model and immunohistochemistry results indicated that circ_0001946 inhibited GBM growth as well as the expression of Ki67 in GBM cells. Conclusion Our study confirmed that the circ_0001946/miR‐671‐5p/ CDR1 pathway modulates the development of GBM, and this pathway might be a promising target for the development of therapeutics for GBM. The results of our study demonstrated that circ_0001946 could sponge miR‐671‐5p and restrain glioblastoma (GBM) cell malignancy. The activation of the circ_0001946/miR‐671‐5p/cerebellar degeneration‐related autoantigen 1 (CDR1) axis may be a potential therapeutic target and contribute to the treatment of human GBM.