The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy

Behnam, Mohammad; Motamedzadeh, Alireza; Aalinezhad, Marzieh; Dadgostar, Ehsan; Noshabad, Fatemeh Zahra Rashidi; Pourfridoni, Mohammad; Raei, Maedeh; Mirzaei, Hamed; Aschner, Michael; Tamtaji, Omid Reza

doi:10.1007/s11033-022-07656-y

Cited by 7 publications

(3 citation statements)

References 80 publications

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“…The relationship between AQP4 and brain tumor characteristics, such as invasion and migration, has been established. Notably, it was shown that inhibition of AQP4 mitigates the progression of brain tumors [ 48 ]. CPXM2 involvement in tumorigenesis or progression is less consistent.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Spinelli,

Kajana,

Garbarino

et al. 2024

Cancers

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Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Spinelli,

Kajana,

Garbarino

et al. 2024

Cancers

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“…Aquaporin-4 (AQP4) is a critical molecule in the central nervous system that participated in preserving water and ion homeostasis and has been indicated to play a key role in tumor cell invasion [ 192 ]. AQP4 is also associated with α-syntrophin which interacts with the actin cytoskeleton and β-dystroglycan.…”

Section: Structural Factorsmentioning

confidence: 99%

Molecular mechanisms of microRNA-216a during tumor progression

et al. 2023

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MicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.

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“…They found that the reduction in AQP4ex, leading to reduction and delocalization of AQP4, could be likely to undermine the integrity of the BBB, indicating that AQP4ex could be considered as a potential new early biomarker of GBM progression and a target for AQP4 modulation ( Frigeri et al, 2007 ). Various studies have confirmed that AQP4 plays a vital role in GBM’s malignant progression and drug resistance ( Valente et al, 2022 ), but its molecular mechanism still needs more in-depth and comprehensive research ( Peng et al, 2020 ; Behnam et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients

Lan

Nie

Zou

2022

Front. Cell. Neurosci.

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Recent studies have revealed the critical role of AQP4 in the occurrence and development of gliomas. However, the role of AQP4 in immune regulation has not yet been reported. Many recent reports have identified the lymphatic system’s occurrence within the central nervous system (CNS) and the vital role of immune regulation in treating brain tumors. Therefore, the present study aimed to explore the role of AQP4 in the immune regulation of glioma. We used bioinformatics analysis to investigate the immunoregulatory function of AQP4, including its correlation with immunity, anti-tumor immune processes, immunotherapy, immune infiltration, tumor mutational burden (TMB), stemness, mutation, and pan-cancer. The results revealed that AQP4 was significantly associated with the expression of multiple immune checkpoints, immune cells, as well as multiple immune cell effector genes, and antigen presentation and processing abilities. Although no significant correlation was found between the AQP4 gene and IDH mutation and MGMT, AQP4 demonstrated substantial expression differences in different immunophenotypes and molecular types. Using the TTD database, we discovered that EGFR, ABAT, and PDGFRA are strongly associated with AQP4 expression in the glioblastoma (GBM) classification, and these factors could be the potential AQP4-related immunotherapy targets. Afterward, we screened the differential genes in the high and low AQP4 gene expression group, the high and low immune score group, and the high and low matrix score group and took the intersection as the candidate factor. Finally, univariate Cox analysis was used to find eight prognostic variables with significant differences across the candidate genes. After lasso dimensionality reduction, three genes built the model (RARRES1, SOCS3, and TTYH1). The scoring model generated by the three genes was eventually obtained after the multi-factor screening of the three genes. Finally, combined with clinical information and cox regression analysis, it was further confirmed that the model score could be used as an independent prognostic factor.

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The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy

Cited by 7 publications

References 80 publications

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Molecular mechanisms of microRNA-216a during tumor progression

Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients

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