Glioma Radioresistance Research Articles

Inhibitor of Wnt receptor 1 suppresses the effects of Wnt1, Wnt3a and β‑catenin on the proliferation and migration of C6 GSCs induced by low‑dose radiation.

The radioresistance of glioma is an important cause of treatment failure and tumor aggressiveness. In the present study, under performed with linear accelerator, the effects of 0.3 and 3.0Gy low‑dose radiation (LDR) on the proliferation and migration of C6 glioma stem cells invitro were examined by flow cytometric analysis, immunocytochemistry and western blot analysis. It was found that low‑dose ionizing radiation (0.3Gy) stimulated the proliferation and migration of these cells, while 3.0Gy ionizing radiation inhibited the proliferation of C6 glioma stem cells, which was mediated through enhanced Wnt/β‑catenin signaling, which is associated with glioma tumor aggressiveness. LDR treatment increased the expression of the DNA damage marker γ‑H2AX but promoted cell survival with a significant reduction in apoptotic and necrotic cells. When LDR cells were also treated with an inhibitor of Wnt receptor 1 (IWR1), cell proliferation and migration were significantly reduced. IWR1 treatment significantly inhibited Wnt1, Wnt3a and β‑catenin protein expression. Collectively, the current results demonstrated that IWR1 treatment effectively radio‑sensitizes glioma stem cells and helps to overcome the survival advantages promoted by LDR, which has significant implications for targeted treatment in radioresistant gliomas.

Reactive astrocytes and glioblastoma: are there new targets for more effective antitumor therapy?

Introduction. Astrocytes in the brain of a healthy person perform a number of protective functions, contribute to maintaining the functional activity of neurons and their synapses. However, in some pathological conditions, they change their phenotype to a reactive one and can both remodel damaged areas and contribute to increased aggression and invasiveness of gliomas.Aim. To comprehensively study the features of reactive astrocytes and the chemo- and radioresistance of gliomas associated with reactive astrocytes.Materials and methods. The authors analyzed articles from the databases Elsevier, pubmed, Scopus, google Scholar, Embase, web of Science, The Cochrane Library, global Health, CyberLeninka and RSCI. when selecting articles, the indexing systems of journals and the citation of articles, the scientific novelty of research, the statistical significance of the results obtained in them were taken into account, publications with duplication of the results of previous studies were excluded. In the course of the study, data on the mutual influence of reactive astrocytes and glioma cells were systematized.Results. Astrocytes of the brain of healthy people are highly variable and heterogeneous, which further complicates the interpretation of published studies. At the same time, reactive astrocytes contribute to an increase in the chemoresistance and radioresistance of gliomas of different degrees of malignancy. At the same time, the exact mechanisms for controlling the interaction between reactive astrocytes and glioma cells, which contributed to less progression and invasion of the tumor or its regression, have not yet been established. However, this direction is now actively developing and is promising due to the possibility of additional effects on gliomas.Conclusion. At the moment, there is no effective treatment that can cope with gliomas, all existing treatment methods are aimed only at increasing the life expectancy of patients with gliomas. The results of recent studies suggest that, probably, the current insufficient effectiveness of chemo- and radiotherapy may be associated with a very close relationship between tumor cells and tumor-associated reactive astrocytes due to their mutual supportive effect. Therefore, the solution to the problem of incurable patients with gliomas may lie in a complex effect on both tumor cells and their microenvironment.

Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma.

Tumor-initiating cells contained within the aggressive brain tumor glioma (glioma stem cells, GSCs) promote radioresistance and disease recurrence. However, mechanisms of resistance are not well understood. Herein, we show that the proteome-level regulation occurring upon radiation treatment of several patient-derived GSC lines predicts their resistance status, whereas glioma transcriptional subtypes do not. We identify a mechanism of radioresistance mediated by the transfer of the metabolic enzyme NAMPT to radiosensitive cells through microvesicles (NAMPT-high MVs) shed by resistant GSCs. NAMPT-high MVs rescue the proliferation of radiosensitive GSCs and fibroblasts upon irradiation, and upon treatment with a radiomimetic drug or low serum, and increase intracellular NAD(H) levels. Finally, we show that the presence of NAMPT within the MVs and its enzymatic activity in recipient cells are necessary to mediate these effects. Collectively, we demonstrate that the proteome of GSCs provides unique information as it predicts the ability of glioma to resist radiation treatment. Furthermore, we establish NAMPT transfer via MVs as a mechanism for rescuing the proliferation of radiosensitive cells upon irradiation.

MiR-320b aberrant expression enhances the radioresistance of human glioma via upregulated expression of ALDH1A3.

Accumulating evidence has demonstrated that ALDH1A3 is closely associated with development, progression, radioresistance and prognosis in a variety of cancers. However, the upstream miRNA that plays in the ALDH1A3 signaling pathways in regulating the radioresistance of glioma remains unclear. In this study, ALDH1A3 was enriched in high-grade glioma and was determined to be essential for radioresistance in GBM cell lines. Moreover, miR-320b was identified as an upstream miRNA that interacts with ALDH1A3. Low expression of miR-320b was associated with poor prognosis and radioresistance in glioma. In addition, overexpression of miR-320b counteracted the effects of ALDH1A3 on GBM cell proliferation, apoptosis and radioresistance when exposed to X-ray irradiation. Collectively, miR-320b may serve as a novel therapeutic target for glioma patients.

PLK1 inhibition promotes apoptosis and DNA damage in glioma stem cells by regulating the nuclear translocation of YBX1

Glioma stem cells (GSCs) are the important cause of tumorigenesis, recurrence, and chemo(radio)resistance in glioma. Targeting GSCs helps improve the outcomes of glioma treatment. Polo-like kinase 1 (PLK1) is a member of the serine/threonine protein kinase family, which is highly conserved. In recent years, it has been suggested that increased levels of PLK1 and its activity are associated with tumor progression and poor prognosis. We aimed to identify whether PLK1 plays a critical role in stemness maintenance and apoptosis regulation in GSCs. Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1. Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs. We confirmed that YBX1 knockdown resulted in the apoptosis and DNA damage of GSCs. These findings uncover that PLK1 inhibition induces cell apoptosis and DNA damage in GSCs through YBX1 phosphorylation, providing new insights into the mechanism by which PLK1 inhibition contributes to the apoptosis of and DNA damage in gliomas.

PGC1α Degradation Suppresses Mitochondrial Biogenesis to Confer Radiation Resistance in Glioma.

Glioma cells reduce mitochondrial biogenesis by promoting PGC1α degradation to promote resistance to radiotherapy, indicating potential therapeutic strategies to enhance radiosensitivity.

Most recent update of preclinical and clinical data on radioresistance and radiosensitivity of high-grade gliomas-aradiation oncologist's perspective.

This review article discusses the studies concerning advances in radiotherapy of high-grade gliomas published in the second half of 2021. Aliterature search was performed in PubMed using the terms ("gliom* and radio*") and time limits 1July 2021-31December 2021. The articles were then manually selected for relevance to the analyzed topics. Considerable progress has been made in the preclinical field on the mechanisms of radioresistance and radiosensitization of high-grade gliomas (HGG). However, fewer early-phase (I/II) clinical trials have been performed and, of the latter, even fewer have produced results that justify moving to phaseIII. In the 6‑month period under consideration, no studies were published that would lead to achange in clinical practice and the overall survival (OS) of patients remained similar to that of 2005, the year in which it increased significantly for the last time thanks to introduction of the alkylating agent temozolomide. After 17years of stalemate in improving the OS of patients with HGG, an in-depth analysis of the causes should be carried out in order to identify whether the research efforts conducted so far, including in the radiotherapeutic field, have been the most effective or require improvement. In our opinion, in addition to the therapeutic difficulties related to the biology of HGG tumors (e.g., high infiltrating capacity, multiple resistance mechanisms, blood-brain barrier), some public research policy choices may also play arole, especially in consideration of the limited interest of the pharmaceutical industry in the field of rare cancers.

Emerging roles of ferroptosis in glioma.

Glioma is the most common primary malignant tumor in the central nervous system, and directly affects the quality of life and cognitive function of patients. Ferroptosis, is a new form of regulated cell death characterized by iron-dependent lipid peroxidation. Ferroptosis is mainly due to redox imbalance and involves multiple intracellular biology processes, such as iron metabolism, lipid metabolism, and antioxidants synthesis. Induction of ferroptosis could be a new target for glioma treatment, and ferroptosis-related processes are associated with chemoresistance and radioresistance in glioma. In the present review, we provide the characteristics, key regulators and pathways of ferroptosis and the crosstalk between ferroptosis and other programmed cell death in glioma, we also proposed the application and prospect of ferroptosis in the treatment of glioma.

Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma.

Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.

Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling.

Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/β-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/β-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/β-catenin activation. Besides, pharmacological inhibition of Wnt/β-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/β-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients.

LINC01123 potentially correlates with radioresistance in glioma through the miR-151a/CENPB axis.

Radiotherapy represents the most effective nonsurgical therapy, whereas acquired radioresistance remains a major challenge in glioma treatment. Deregulation of long noncoding RNAs (lncRNAs) is frequently involved in tumorigenesis. This study investigates the role of LINC01123 in radioresistance in glioma with molecules involved. LINC01123 was identified as the most upregulated gene in a glioma gene expression dataset GSE103227. LINC01123 was highly expressed in the radioresistant glioma tissues radioresistant glioma U251 (U251R) cells. Downregulation of LINC01123 reduced cell proliferation and colony formation abilities, as well as resistance to apoptosis of the U251R cells after 4 Gy X-ray irradiation. The micro(mi)RNA-151a gene (miR-151a) was a poorly expressed miRNA in glioma, and it was a target of LINC01123. The centromere protein B gene (CENPB) mRNA was a direct target of miR-151a and demonstrated a positive correlation with LINC01123 in glioma tissues and cells. Further inhibition of miR-151a or overexpression of CENPB restored radioresistance of glioma cells. In addition, silencing of LINC01123 suppressed growth of xenograft tumors formed by U251R cells in nude mice. To conclude, the present study demonstrates that LINC01123 serves as a sponge for miR-151a and upregulates CENPB expression to increase the radioresistance of glioma cells in vitro and in vivo.

Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair

Although radiotherapy is a well-known effective non-surgical treatment for malignant gliomas, the therapeutic efficacy is severely limited due to the radioresistance of tumor cells. Previously, we demonstrated that Yes-associated protein (YAP) promotes glioma malignant progression. However, whether YAP plays a role in radioresistance and its potential value in cancer treatment are still unclear. In this study, we found that high YAP expression is associated with poor prognosis in malignant glioma patients undergoing radiotherapy. Research in immortalized cell lines and primary cells from GBM patients revealed that YAP exhibited a radioresistant effect on gliomas via promoting DNA damage repair. Mechanistically, after radiation, YAP was translocated into the nucleus, where it promoted the expression and secretion of FGF2, leading to MAPK–ERK pathway activation. FGF2 is a novel target gene of YAP. Inhibition of YAP–FGF2–MAPK signaling sensitizes gliomas to radiotherapy and prolongs the survival of intracranial cell-derived and patient-derived xenograft models. These results suggest that YAP–FGF2–MAPK is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy.

LncRNA H19 Upregulation Participates in the Response of Glioma Cells to Radiation.

Previous studies have indicated that radiation resistance of glioma is one of the leading causes of radiotherapy failure. Mounting evidence suggests that long non-coding RNA (lncRNA) plays an important role in regulating radiosensitivity of cancer cells via implicating in various cell processes. However, the underlying mechanisms remain unclear and need further study, especially at the molecular level. We found that the expression level of lncRNA H19 was elevated by radiation, and then, the modulation of H19 affected the resistant of glioma cells to X-rays. Dual-luciferase reporter analyses showed that H19 was transcriptionally activated by CREB1 in glioma cells after irradiation. In addition, both flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) assay suggested that H19 was involved in the cell cycle arrest, apoptosis, and DNA synthesis to modulate the radiation response of glioma cells and influenced their radioresistance. Therefore, H19 might play a crucial role in enhancing the radioresistance of glioma.

Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating microRNA-128 in Gliomas.

IntroductionGlioma is the most common malignant brain tumor in adults. Radiation is a key therapy in glioma. However, the radioresistance of glioma was a big challenge. HLA complex P5 (HCP5) has been reported dysregulated in several types of malignant tumor, including glioma. The role of HCP5 in the radiosensitivity of glioma is so far unknown. The present study aimed to investigate the effect of HCP5 on radiosensitivity in gliomas.MethodsThe levels of HCP5 and microRNA (miR)-128 were detected using qRT-PCR. The cell growth curve was used to show the cell proliferation and evaluate the radiosensitivity of glioma cells following exposure to X-ray. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to test the cellular senescence. Luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to determine the correlation between HCP5 and miR-128.ResultsHCP5 level of glioma cells was significantly higher than human astrocytes, whereas miR-128 level was lower in glioma cells. Besides, the HCP5 expression was increased in glioma tissues compared to normal brain tissues (NBTs). Knockdown of HCP5 inhibited cell proliferation and increased radiosensitivity in glioma cells. MiR-128 was predicted to be a target of HCP5. It was demonstrated that HCP5 directly bound to miR-128 and regulated its expression in glioma cells. Furthermore, the effects of HCP5 knockdown on radiosensitivity of glioma cells were attenuated by the inhibitor of miR-128.ConclusionThese findings suggested that interaction between lncRNA HCP5 and microRNA-128 could regulate the radiosensitivity of glioma cells by intervening in cellular senescence. This might be used as the potential radio-sensitization targets for glioma therapy.

FOXG1 mediates the radiosensitivity of glioma cells through regulation of autophagy

Background/Aim Upregulation of Forkhead box G1 (FOXG1) has recently been observed in many cancers, while its effect on radiosensitivity in glioma is still unclear. In this study, we hypothesized that FOXG1 be a major player in radioresistance of glioma as well as the underlying mechanism. Methods Immunohistochemistry (IHC) was conducted to assess FOXG1 expression in glioma tissues and glioma-adjacent tissues. Western Blot was implemented to detect the expression of autophagy-related proteins. CCK-8, colony formation and flow cytometry assays were implemented to assess cell viability, proliferation and apoptosis, respectively. Transmission electron microscope (TEM) was used to observe autophagic vesicles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was applied to detect the expression of FOXG1. Results The present study demonstrated that FOXG1 was highly expressed in glioma tissues. FOXG1 expression level was up-regulated in glioma cells following exposure to X-ray irradiation. FOXG1 can attenuate radiosensitivity of glioma cells. Moreover, it revealed that FOXG1 attenuate radiosensitivity of glioma cells by promoting autophagy. Conclusions The present study suggests that FOXG1 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy, and it may be a target for the treatment of human brain glioma.

LncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR‑106a‑5p‑mediated P38 MAPK signaling.

Glioma is diagnosed as the most common intracranial malignant tumor. Cancer stem cells determine stemness and radioresistance, and may facilitate glioma recurrence. The present study aimed to investigate whether the long non-coding RNA (lncRNA) transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) regulated cell stemness and radioresistance of glioma, and determine the underlying molecular mechanism of TPTEP1 in the modulation of glioma progression. Cell and molecular biology techniques were applied for investigating the role of TPTEP1 in glioma cell lines, animal model, and clinical samples. The results demonstrated that TPTEP1 attenuated stemness and radioresistance of glioma both in vitro and in vivo. In addition, TPTEP1 augmented MAPK14 expression by competitively interacting with microRNA (miR)-106a-5p, thus activating the P38 MAPK signaling pathway, and suppressing glioma stemness and radioresistance. TPTEP1 functionally bound to miR-106a-5p, which formed a reciprocal regulatory loop to stimulate the P38 MAPK signaling pathway. Low TPTEP1 expression levels were detected in high-grade glioma tissues compared with low-grade glioma tissues, and were positively associated with poor prognosis of patients with glioma. Furthermore, analysis using data from The Cancer Genome Atlas database confirmed the molecular mechanism and biological significance of dysregulation of TPTEP1 in glioma progression. Taken together, the results of the present study suggest that TPTEP1 may be applied as a diagnostic and prognostic indicator for glioma, and may be an alternative target for the treatment of glioma.

Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.

Long Noncoding RNA TP53TG1 Contributes to Radioresistance of Glioma Cells Via miR-524-5p/RAB5A Axis.

Background: Long noncoding RNAs (lncRNAs) have been reported to be important regulators in cancer. In this study, we aimed to discover the functions of lncRNA TP53TG1 in glioma. Methods: The expression of lncRNA TP53TG1, microRNA-524-5p (miR-524-5p) and RAB5A, a member RAS oncogene family (RAB5A), were examined by quantitative real-time polymerase chain reaction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were applied to analyze the proliferation and apoptosis of glioma cells. Colony formation assay was used to detect the colony formation ability and radioresistance of glioma cells. Western blot assay was performed to detect the expression of autophagy-associated proteins and RAB5A. StarBase software was utilized to predict the combination between miR-524-5p and TP53TG1 or RAB5A, and dual-luciferase reporter assay and RNA immunoprecipitation assay were used to verify the above predictions. Animal experiment using immunodeficient nude mice was conducted to detect the role of TP53TG1 in vivo. Results: Radiation stimulation (6 Gy) upregulated the abundance of TP53TG1. TP53TG1 potentiated radioresistance and progression of glioma by promoting the autophagy. miR-524-5p was verified as a direct downstream regulation of TP53TG1. miR-524-5p depletion attenuated the influence of TP53TG1 interference on the functions of glioma cells. RAB5A was a direct target of miR-524-5p as well. The inhibitory effect of miR-524-5p on the malignancy of glioma cells was overturned by overexpression of RAB5A. RAB5A was regulated by TP53TG1/miR-524-5p signaling in glioma cells. TP53TG1 silencing impeded the progression of glioma in vivo. Conclusion: lncRNA TP53TG1 accelerated the proliferation, colony formation, autophagy, and radioresistance, and restrained the apoptosis of glioma cells through miR-524-5p/RAB5A axis.

Inhibition of mitochondria NADH–Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation

Radiation is a current standard treatment of glioma. The fractionated radiotherapy with low dose of radiation over weeks has been employed in glioma patients, while radiotherapy can only offer palliation due to the radioresistance. We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant glioma cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells, which showed the mitochondria NADH–ubiquinone oxidoreductase (Complex I) subunits were up-regulated in the radioresistant cells. The copy numbers of mitochondria were increased in the radioresistant glioma cells. After using mitochondria Complex I inhibitors, rotenone and metformin, to treat glioma cells, we found the resistant glioma cells re-sensitized to radiation. These results demonstrate that Complex I is associated with the fractioned radiation-induced radioresistance of glioma and would be a potent target for clinical radiotherapy of glioma.

The circ_VCAN with radioresistance contributes to the carcinogenesis of glioma by regulating microRNA-1183.

Circular RNAs (circRNAs), a widespread type of noncoding RNA, are produced by reverse splicing with a circular loop structure. Circ_VCAN (hsa_circ_0073237) acts as a novel circRNA, although its roles in the progression and radioresistance of glioma remain unknown.Expressions of circ_VCAN and microRNA-1183 (miR-1183) were analyzed by quantitative real-time PCR, and the functions of circ_VCAN and irradiate in glioma cell proliferation, apoptosis, migration, and invasion were assessed using cell counting kit-8, flow cytometry, Wound healing, and Transwell assays. The interaction between circ_VCAN and miR-1183 was validated dual-luciferase reporter assay.Our results revealed that circ_VCAN was significantly upregulated in radioresistant glioma tissues compared with radiosensitive tissues, and that circ_VCAN expression was negatively correlated with miR-1183 expression in glioma tissues. We also determined that circ_VCAN expression was decreased and miR-1183 expression was increased in U87 and U251 cells after irradiation. Both knockdown of circ_VCAN and treatment with miR-1183 mimics inhibited proliferation, migration, and invasion, and accelerated apoptosis of the irradiated U87 and U251 cells. In addition, luciferase reporter assays revealed that circ_VCAN might function as a sponge for miR-1183. Finally, overexpression of circ_VCAN expedited carcinogenesis and reduced glioma radiosensitivity by regulating miR-1183.Circ_VCAN serves as a potential oncogene of glioma by regulating miR-1183, and plays an essential role in the radioresistance of glioma.