Xinxing Li1, Hongyu Diao1. 1. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Abstract
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.
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.