NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

Zeng, Zhaomu; Chen, Yueyue; Geng, Xiuchao; Zhang, Yuhao; Wen, Xichao; Yan, Qingyu; Wang, Tingting; Li, Qiang; Xu, Yawei; Duan, Junchao; Zheng, Kewen; Sun, Zhonghua

doi:10.3892/ijo.2022.5366

Cited by 12 publications

(8 citation statements)

References 182 publications

(200 reference statements)

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“…In recent years, increasing studies have found that various circRNAs are abnormally expressed in GBM, which are involved in the occurrence, development and malignant progression of GBM [ 30 ]. CircASAP1 expression was significantly upregulated in GBM and promotes tumorigenesis and temozolomide resistance of GBM via NRAS/MEK1/ERK1-2 signaling [ 31 ].…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Throughout the process of glioma treatment, doctors select methods depending on several factors, such as the type of brain tumour, the location and size of the tumour, and the patient's overall health. Treatment methods include surgery 21 , radiation therapy 22 , chemotherapy 23 , targeted therapy 24 , immunotherapy 25 , and supportive care 26 . Surgery is often the first step in treatment.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Exploration of Structure‒Function Crosstalk in Glioma: Protein Structuromics

Xiao

Yang

Wang

et al. 2023

Preprint

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Glioma is a type of tumour that starts in the glial cells of the brain or the spine. Since the 1800s, when the disease was first named, survival rates have always been unsatisfactory. Despite great advances in molecular biology and traditional treatment methods, many questions remain to be answered regarding cancer occurrence and the underlying mechanism. Medical doctors remain stymied regarding tumour recurrence and worsening disease after effective treatment. To better understand the relevant questions, in this study, 20 oncogenes and 20 anti-oncogenes were examined in relation to protein structure, from protein structure analysis and dynamic analysis methods to 3D structure analysis and systematic analysis of the structure‒ function relationships of proteins. We hope that these analyses will help promote mechanistic research and the development of new treatments for glioma.

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“…Compared with linear RNA, its tissue expression is stable and not easy to degrade [ 18 ]. With the wide application of high-throughput sequencing technology, a large number of circRNAs have been found in GBM and other malignant tumors [ 19 ]. Our previous study found that circCHAF1A promotes the proliferation and tumorigenesis of GSCs via MDM2-dependent p53 signaling [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

CircKPNB1 mediates a positive feedback loop and promotes the malignant phenotypes of GSCs via TNF-α/NF-κB signaling

et al. 2022

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Glioma stem cells (GSCs) are a special kind of cells in GBM showing tumor initiation, self-renewal, and multi-lineage differentiation abilities. Finding novel circRNAs related to GSCs is of great significance for the study of glioma. qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of circKPNB1, SPI1, DGCR8, and TNF-α. The expression of these molecules in GSCs was regulated by lentiviral-based infection. RNA immunoprecipitation assay, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to study the direct regulation mechanisms among these molecules. All the MTS, EDU, transwell, neurosphere formation assays, ELDA assays, and xenograft experiments were used to detect the malignant phenotype of GSCs. We found a novel circRNA circKPNB1 was overexpressed in GBM and associated with GBM patients’ poor prognosis. CircKPNB1 overexpression can promote the cell viabilities, proliferation, invasion, neurospheres formation abilities, and stemness of GSCs. Mechanistically, circKPNB1 regulates the protein stability and nuclear translocation of SPI1. SPI1 promotes the malignant phenotype of GSCs via TNF-α mediated NF-κB signaling. SPI1 can also transcriptionally upregulate DGCR8 expression, and the latter can maintain the stability of circKPNB1 and forms a positive feedback loop among DGCR8, circKPNB1 and SPI1. Our study found circKPNB1 was a novel oncogene in GBM and of great significance in the diagnosis and prognosis prediction of GBM and maybe a novel target for molecular targeted therapy.

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NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

Cited by 12 publications

References 182 publications

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

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

Preliminary Exploration of Structure‒Function Crosstalk in Glioma: Protein Structuromics

CircKPNB1 mediates a positive feedback loop and promotes the malignant phenotypes of GSCs via TNF-α/NF-κB signaling

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