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Circ_0021350 plays an oncogene role by regulating miR-1207-3p/ PIK3R3 in glioblastoma

ABSTRACT: To screen differentially expressed circRNAs in GBM, we performed RNA-seq using four tumor tissues from patients with GBM and four normal brain tissues and focused on circ_0021350, which is upregulated in GBM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222421 | GEO | 2024/01/10

REPOSITORIES: GEO

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Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma.

Project description:BackgroundGlioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM.MethodsRNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors.ResultsCirc_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350.ConclusionOur findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.

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Gene expression in glioblastoma (GBM) tissues, glioblastoma stem-like cell (GSC) cultures and neural foetal cell line (NFC)

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Circ_0021350 plays an oncogene role by regulating miR-1207-3p/ PIK3R3 in glioblastoma

Project description:Circ_0021350 plays an oncogene role by regulating miR-1207-3p/ PIK3R3 in glioblastoma

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Silencing of circRNA Igf1r plays a protective role in neuronal injury via regulating astrocyte polarization during epilepsy

Project description:To identify epilepsy-related circular RNAs, we used three mice brain tissues of status epilepticus models and paired control brain tissues for RNA sequencing. Differential expressions of circRNAs were then analyzed.

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Comparison of glioblastoma cell culture platforms based on transcriptional similarity with paired tissue

Project description:In this study, we isolated GBM TSs and extracellular matrices (ECM) from tissues obtained from newly diagnosed IDH1 wild-type GBM patients, and cultured GBM TSs on five different culture platforms: (1) ordinary TS culture liquid media (LM), (2) collagen-based three-dimensional (3D) matrix, (3) patient normal ECM-based 3D matrix, (4) patient tumor ECM-based 3D matrix, and (5) mouse brain. To evaluate each culture platform, we obtained transcriptome data of all cultured GBM TSs using microarrays. The LM platform exhibited the most similar transcriptional program to paired tissues based on the four aspects, including GBM genes, stemness- and invasiveness-related genes, transcription factor activity, and canonical signaling pathways. GBM TSs can be cultured via an easy-to-handle, cost-efficient, and time-saving LM platform while preserving the transcriptional program of the originating tissues without supplementing artificially manipulated or patient-derived ECM or embedding into the mouse brain to imitate the tumor microenvironment of brain. In addition to applications in basic cancer research, GBM TSs cultured in LM may also serve as patient avatars in drug screening and pre-clinical evaluation of targeted therapy, and may function as a standardized and clinically relevant model for precision medicine owing to its scalability and reproducibility.

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INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme

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CRISPRi Screen of Long Non-coding RNAs Identifies LINC03045 Regulating Glioblastoma Invasion

Project description:Introduction: Glioblastoma (GBM) invasion studies have focused on coding genes, while few studies evaluate long non-coding RNAs (lncRNAs), transcripts without protein-coding potential, for role in GBM invasion. We leveraged CRISPR-interference (CRISPRi) to evaluate invasive function of GBM-associated lncRNAs in an unbiased functional screen, characterizing and exploring the mechanism of identified candidates. Methods: We implemented a CRISPRi lncRNA loss-of-function screen evaluating association of lncRNA knockdown (KD) with invasion capacity in Matrigel. Top screen candidates were validated using CRISPRi and oligonucleotide(ASO)-mediated knockdown in three tumor lines. Clinical relevance of candidates was assessed via The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx) survival analysis. Mediators of lncRNA effect were identified via differential expression analysis following lncRNA KD and assessed for tumor invasion using knockdown and rescue experiments. Results: Forty-eight lncRNAs were significantly associated with 33-83% decrease in invasion (p<0.01) upon knockdown. The top candidate, LINC03045, identified from effect size and p-value, demonstrated 82.7% decrease in tumor cell invasion upon knockdown, while LINC03045 expression was significantly associated with patient survival and tumor grade(p<0.0001). RNAseq analysis of LINC03045 knockdown revealed that WASF3, previously implicated in tumor invasion studies, was highly correlated with lncRNA expression, while WASF3 KD was associated with significant decrease in invasion. Finally, WASF3 overexpression demonstrated rescue of invasive function lost with LINC03045 KD. Conclusion: CRISPRi screening identified LINC03045, a previously unannotated lncRNA, as critical to GBM invasion. Gene expression is significantly associated with tumor grade and survival. RNA-seq and mechanistic studies suggest that this novel lncRNA may regulate invasion via WASF3.

2024-06-03 | GSE268342 | GEO

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