Research Progress of circRNAs in Glioblastoma

Guo, Xu; Piao, Haozhe

doi:10.3389/fcell.2021.791892

Cited by 14 publications

(9 citation statements)

References 173 publications

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“…Circular RNAs (circRNAs) are a particular class of non-coding RNAs (ncRNAs), which form a circular structure by covalent bonds without a 5’ end cap and 3’ end poly (A) tail in linear RNAs [ 5 ]. CircRNAs are characterized by high stability, abundance, and conservation in all kinds of human tissues, especially in brains [ 6 ]. Abnormal expression of circRNAs is found in glioma, gastric cancer, pancreatic cancer and other tumors, and they are reported to play a vital role in the progression, metastasis and other malignant phenotypes of tumors [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

Jiang

Zhao

et al. 2022

J Exp Clin Cancer Res

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Background Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression of glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles in ferroptosis via several mechanisms, including regulating iron metabolism, glutathione metabolism, lipid peroxidation and mitochondrial-related proteins, there are many novel circRNAs regulating ferroptosis need to be found, and they may become a new molecular treatment target in GBM. Methods The expression levels of circLRFN5, PRRX2 and GCH1 were detected by qPCR, western blotting, and immunohistochemistry. Lentiviral-based infections were used to overexpress or knockdown these molecules in glioma stem cells (GSCs). The biological functions of these molecules on GSCs were detected by MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), the 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) and xenograft experiments. The content of ferroptosis levels in GSCs was detected by BODIPY 581/591 C11 assay, glutathione (GSH) assay and malondialdehyde (MDA) assay. The regulating mechanisms among these molecules were studied by RNA immunoprecipitation assay, RNA pull-down assay, ubiquitination assay, dual-luciferase reporter assay and chromatin immunoprecipitation assay. Results We found a novel circRNA circLRFN5 is downregulated in GBM and associated with GBM patients’ poor prognosis. CircLRFN5 overexpression inhibits the cell viabilities, proliferation, neurospheres formation, stemness and tumorigenesis of GSCs via inducing ferroptosis. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4). Conclusions Our study found circLRFN5 as a tumor-suppressive circRNA and identified its role in the progression of ferroptosis and GBM. CircLRFN5 can be used as a potential GBM biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM.

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Section: Introductionmentioning

confidence: 99%

CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

Jiang

Zhao

et al. 2022

J Exp Clin Cancer Res

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“…Several studies have implicated circRNAs to regulate physiological conditions and disease progression [ 37 ]. Numerous investigators have shown that circRNAs are involved in brain-related disorders such as Alzheimer’s disease [ 38 , 39 ], Parkinson’s disease [ 40 ], and glioblastoma [ 41 ]. Secondly, circRNAs are also highly expressed in the heart.…”

Section: Discussionmentioning

confidence: 99%

Role of circular RNA cdr1as in modulation of macrophage phenotype

et al. 2022

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“…Recently, circRNAs have become more attention as new prognostic or therapeutic targets for tumors. CircRNAs were found to be differentially expressed in GBM [25][26][27][28][29][30][31][32]. In addition, previous research showed that circRNA was regulated by HIF-1α under hypoxia condition.…”

Section: Discussionmentioning

confidence: 99%

“…The differences of circRNAs' distribution chromosomes including chr8 (12 vs 4), chr17 (26 vs 8), chr18 (5 vs 12), chrX (2 vs 13) and chrM (0 vs 8) between in upregulated and downregulated groups were more than doubled. The upregulated circRNAs were most distributed on chr3 (30). The downregulated circRNAs were most distributed on chr1 (34).…”

Section: Figuresmentioning

confidence: 97%

Profiling and Bioinformatics Analyses of Differential Circular RNA Expression in Glioblastoma Multiforme Cells Under Hypoxia

Chen

Yang

et al. 2022

J Mol Neurosci

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BackgroundThe hypoxia microenvironment is highly associated with GBM's malignant phenotypes. CircRNAs were reported involved in GBM's biological characteristics and regulated by HIF-1α. However, the differential expression pro le and role of circRNAs in GBM cells under hypoxia are still unclear. MethodsThe expression pro les of circRNAs in LN229 and T98G under hypoxia were explored via circRNA sequencing analysis. Those circRNAs signi cantly dysregulated both in LN229 and T98G, and could be found in circBase were selected and validated by qRT-PCR, RNase R digestion reaction and Sanger sequencing. Normal cell line and fresh GBM tissues were also used for qRT-PCR validation. The roles of differentially expressed circRNAs were evaluated by bioinformatics analyses. ResultsThere were 672 dysregulated circRNAs in LN229 and 698 dysregulated circRNAs in T98G. GO analysis indicated that the alteration of circRNAs expression related to GBM cell's biogenesis and metabolism. KEGG analysis demonstrated that TGF-β signaling pathway, HIF-1 signaling pathway and metabolism related signaling pathway were closely associated with differentially expressed circRNAs under hypoxia.These results were con rmed by GSEA analysis. The 6 selected and dysregulated circRNAs both in LN229 and T98G including hsa_circ_0000745, hsa_circ_0020093, hsa_circ_0020094, hsa_circ_0000943, hsa_circ_0004874 and hsa_circ_0002359 were validated by qRT-PCR. Inhibition of hsa_circ_0000745 inhibited GBM cell's proliferation, migration and invasion. HIF-1α centered circRNA-miRNA-mRNA networks analysis showed that the 6 validated circRNAs could cross-talk with 11 related miRNAs. ConclusionThe circRNA expressions are dysregulated in GBM cell under hypoxia. The 6 validated circRNAs could participate in GBM's development and progression when hypoxia occurs. They might be the candidates for prognostic markers and adjuvant therapeutics of GBM in the future.

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Research Progress of circRNAs in Glioblastoma

Cited by 14 publications

References 173 publications

CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

Role of circular RNA cdr1as in modulation of macrophage phenotype

Profiling and Bioinformatics Analyses of Differential Circular RNA Expression in Glioblastoma Multiforme Cells Under Hypoxia

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