Circular RNA circ_0001946 acts as a competing endogenous RNA to inhibit glioblastoma progression by modulating miR-671-5p and <it><bold>CDR1</it></bold>

被引:95
作者
Li, Xinxing [1 ]
Diao, Hongyu [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Neurosurg, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China
关键词
cerebellar degeneration-related autoantigen 1 (CDR1); circ_0001946; glioblastoma; miR-671-5p; proliferation; CELL-PROLIFERATION; EXPRESSION; CANCER; KI-67; MULTIFORME; AXIS;
D O I
10.1002/jcp.28061
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
ObjectivesIn 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. MethodsMicroarrays 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. ResultsThe 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. ConclusionOur 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.
引用
收藏
页码:13807 / 13819
页数:13
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