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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Circular RNA circNRIP1 promotes glioma progression by regulating the miR-106a-5p/GPR133 pathway
Shiyuan Zhang1, Wei Huang1, Jimin He1
1Department of Neurosurgery, Suining Central Hospital, Suining, 629099, Sichuan, China.
None:
Glioma is one of the most common and aggressive types of brain tumors, characterized by generally low survival rates. Circular RNAs (circRNAs) have been identified as key players in the development of glioma. Our study aims to investigate the effect of circNRIP1 on glioma progression and elucidate the underlying mechanisms involved. The mRNA expression of circNRIP1, miR-106a-5p, and GPR133 was determined using qRT-PCR. The protein expression of N-cadherin, E-cadherin, fibronectin, vimentin, and GPR133 in glioma cells and tissues was measured through Western blotting and IHC assays. Cell counting kit-8 (CCK-8), wound healing, and transwell assays were used to determine cell proliferation, migration, and invasion, respectively. The dual-luciferase reporter assay was utilized to elucidate the targeting interaction between miR-106a-5p and both circNRIP1 and GPR133. Finally, xenograft models were established to investigate the effects of circNRIP1 in vivo. The expression of circNRIP1 was significantly elevated in glioma cell lines and tissues, and this higher expression correlated with a reduced overall survival rate. Downregulation of circNRIP1 had been shown to inhibit the invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT) of glioma cells and attenuate tumor growth in vivo. circNRIP1 functions as a molecular sponge for miR-106a-5p, consequently elevating the expression of GPR133. Additionally, upregulation of GPR133 could counteract the inhibition of the malignant phenotype of glioma cells caused by circNRIP1 knockdown. circNRIP1 knockdown suppresses glioma progression by elevating miR-106a-5p levels and simultaneously reducing GPR133 expression. The identified circNRIP1/miR-106a-5p/GPR133 axis could potentially be a therapeutic target for glioma.
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