Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways

Han, Xinxin; Jin, Shengkai; Yu, Liming; Wang, Min; Hu, Xinyu; Hu, Daiyu; Ren, Jie; Zhang, Menghan; Huang, Wei; Deng, Jiajia; Chen, Qingqing; Gao, Zhengliang; He, Hua; Cai, Chunhui

doi:10.1186/s13619-022-00123-w

Cited by 4 publications

(2 citation statements)

References 62 publications

(84 reference statements)

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“…At the same time, by conducting enrichment analysis, we explained the molecules potentially interacting with TMEM91 are mainly involved in response to interferon − beta/regulation of viral entry into host cell/modulation by symbiont of entry into host /regulation of viral genome replication/negative regulation of viral process/type I interferon signaling pathway. These processes also indicated the signi cant involvement of TMEM91 in the progression of tumors [25][26][27][28][29] , by reading the literature. Then, we identi ed the relationship between TMEM91 expression and medication response.…”

Section: Discussionmentioning

confidence: 95%

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

Jiang

Song

2023

Preprint

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Transmembrane protein 91(TMEM91) encodes a protein belonging to the transmembrane protein family which mediates many human physiological processes, such as the regulation of cell migration and invasion, and participates in the immune response. At present, research on the TMEM family members focuses mostly on the field of molecular mechanisms, and the role of TMEM91 in tumor cells is still unrecognized. Using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we can analysis the expression of TMEM91 in various tumors. The Kaplan-Meier method was used for the evaluation of the prognostic significance of TMEM91 in patients with pan-cancer. The dif-ferential expression of TMEM91 in diverse cancers with different clinical characteristics was analyzed with the UALCAN database. TIMER was used to explore how TMEM91 correlates with immune infiltration. The correlations between TMEM91 expression immune checkpoint (ICP), tumor mutational burden (TMB), and microsatellite instability (MSI) in human cancers were analyzed via the SangerBox database. Gene Set Cancer Analysis (GSCA) platform was used to investigate the correlation between TMEM91 expression with Copy number variations (CNV) and methylation. Protein-Protein Interaction analysis was performed in the GeneMANIA database. Gene Ontology and Kyoto Encyclopedia of Genes pathway en-richment analyses were further conducted for exploration of TMEM91 function. According to the finding of this study, downregulated TMEM91 expression was observed in numerous tumor tissues. The low TMEM91 expression group showed poor overall survival (OS) and disease-free survival (DFS). TMEM91 was positively correlated with can-cer-associated fibroblast (CAF), and nature killer T cell (NKT), and negatively correlated with CD4 + T cells, B cells and common lymphoid progenitor (CLP). Here, we show that there is a positive relationship between Contingent Negative Variation (CNV) and expression of TMEM91, whereas the correlation of TMEM91 expression with DNA methylation was nega-tive in all cases. Molecular biology experiments were performed to confirm the tumor pro-moting role of TMEM91 in glioma. Function analysis showed that TMEM91 expres-sion-related genes were mainly enriched in response to type I interferon /regulation of viral genome replication/negative regulation of viral process/movement in host environment. In addition, the association between the expression of TMEM91 and the use of the anticancer drug, sensitive anti-tumor drug based on CellMiner were predicted, such as the anticancer drug AS-703569, Hydroxyurea. Our pan-cancer analysis provides a deep understanding of the functions of TMEM91.TMEM91 may affect the oncogenesis and metastasis in different cancers via mediating the immune infiltrating cells and the degree of methylation. This study sheds new light on the mechanism of TMEM family in cancer.

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Section: Discussionmentioning

confidence: 95%

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

Jiang

Song

2023

Preprint

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“…It has been reported that IFN-βinduces G0/G1 phase arrest in human malignant glioma cells by downregulating cyclin A and cyclin-dependent kinase expression. 17 Cyclin A is a necessary regulatory protein in the G1-S phase. Its overexpression will lead to the increase of cells entering the S phase and promote cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

STAT1 negatively regulates human glioma U251 cell proliferation Huang et al: Role of STAT1 in glioma

Huang,

Wang

et al. 2023

Eur J Inflamm

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Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.

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Breaking down the cellular responses to type I interferon neurotoxicity in the brain

Viengkhou

Höfer

2023

Front. Immunol.

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Since their original discovery, type I interferons (IFN-Is) have been closely associated with antiviral immune responses. However, their biological functions go far beyond this role, with balanced IFN-I activity being critical to maintain cellular and tissue homeostasis. Recent findings have uncovered a darker side of IFN-Is whereby chronically elevated levels induce devastating neuroinflammatory and neurodegenerative pathologies. The underlying causes of these ‘interferonopathies’ are diverse and include monogenetic syndromes, autoimmune disorders, as well as chronic infections. The prominent involvement of the CNS in these disorders indicates a particular susceptibility of brain cells to IFN-I toxicity. Here we will discuss the current knowledge of how IFN-Is mediate neurotoxicity in the brain by analyzing the cell-type specific responses to IFN-Is in the CNS, and secondly, by exploring the spectrum of neurological disorders arising from increased IFN-Is. Understanding the nature of IFN-I neurotoxicity is a crucial and fundamental step towards development of new therapeutic strategies for interferonopathies.

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Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways

Cited by 4 publications

References 62 publications

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

A Pan-cancer Analysis of the Role of the Transmembrane Protein 91(TMEM91) in Human Tumors

STAT1 negatively regulates human glioma U251 cell proliferation Huang et al: Role of STAT1 in glioma

Breaking down the cellular responses to type I interferon neurotoxicity in the brain

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