Predictive and prognostic value of TLR9 and NFKBIA gene expression as potential biomarkers for human glioma diagnosis

A, Miyar; Habibi, Iman; Ebrahimi, Ali; Mansourpour, Delaram; Mokarizadeh, Aram; Rajabi, Alireza; Farshgar, Rozhin; Eshaghzadeh, Mehdi; Zamani‐Ahmadmahmudi, Mohamad; Nodushan, Seyed Mohamad Hossein Tabatabaei

doi:10.1016/j.jns.2016.07.046

Cited by 14 publications

(14 citation statements)

References 30 publications

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“…NFKBIA inhibits the activity of dimeric NF-kappa-B/REL complex resulting from masking of their nuclear localization signals. Previous studies have demonstrated that NFKBIA serves as a tumor suppressor in glioblastomas and low expression of NFKBIA is associated with poorer survival in patients [27]. CSF2RB is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF and is weakly expressed in breast cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo

Hong

et al. 2020

J Exp Clin Cancer Res

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Background: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. Methods: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. Results: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. Conclusions: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.

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Section: Discussionmentioning

confidence: 99%

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo

Hong

et al. 2020

J Exp Clin Cancer Res

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“…IκBα is encoded by NFKBIA gene, which is also found abnormal expression involved in human cancer progression. Ata Miyar et al found that NFKBIA expression was decreased in patients with high grad glioma, and the the low expression of NFKBIA is signi cantly related with poor overall survival of glioma patients [12]. Shi et al investigated the mechanism by which HINT1 promotes the stability of inhibitor of NF-κB α (IκBα) in the cytoplasm of hepatocellular carcinoma (HCC) cells and provided new evidence that HINT1 is a regulator of IκBα through SCF (β-TrCP) E3 ligase [25].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, NF-κB is present in an inactive form when it is bound to IκBα, which is encoded by NF-κB inhibitor alpha gene (NFKBIA) [10]. It has been indicated that NFKBIA has identi ed to be involved in carcinogenesis and dysregulated in a variety of cancers, such as head and neck squamous cell carcinoma and glioma [11,12]. However, few studies had been investigated the diagnostic performance of NFKBIA in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

NFKBIA has the Capacity to Serve as a Diagnostic Biomarker for Prostate Cancer Patient

Tao

Gao

et al. 2020

Preprint

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Background: Prostate cancer is the the second leading cause of cancer-related death in male. NF-κB inhibitor alpha gene (NFKBIA), is found dys-expressed in the progression of tumors. The aim of this study was to investigate the expression of NFKBIA and its diagnostic value in prostate cancer patients.Methods: The mRNA expression of NFKBIA was detected with quantitative real-time polymerase chain reaction (qRT-PCR) assay and the association of its expression with clinical characteristic was analyzed via Chi-square test. Receiver operating characteristic (ROC) curve was built to evaluate the diagnostic value of serum NFKBIA.Results: The mRNA expression level of NFKBIA was significantly increased in prostate cancer patients compared with healthy controls (P<0.01). The high expression of NFKBIA was significantly associated with pathological T stage (P=0.010) and differentiation (P=0.019). ROC curve showed that serum NFKBIA had a high diagnostic value in differentiating prostate cancer patients from healthy individuals. The area under the ROC curve (AUC) value was 0.873 corresponding with a sensitivity of 85.6% and a specificity of 78.3%.Conclusions: The expression of NFKBIA was up-regulated in serum of prostate cancer patients and it may be a useful diagnostic bio-maker for the early detection of this cancer.

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“…Human and murine GBM cell lines such as U87-MG, U251-MG, and C6 demonstrated high cell invasion capacity after upregulation of their TLR-9-mediated signal transduction by the receptor agonist CpG dinucleotide [195]. Other studies have proposed the prognostic and diagnostic value of TLR-9 gene expression in GBM patients [196]. In vitro glioma stem cell maintenance was attributed to TLR-9 dependent STAT3 regulation [197].…”

Section: Tlr Expression and Glioma Progressionmentioning

confidence: 97%

Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

Basheer

Abas

Othman

et al. 2021

Cancers

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Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.

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Predictive and prognostic value of TLR9 and NFKBIA gene expression as potential biomarkers for human glioma diagnosis

Cited by 14 publications

References 30 publications

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo

NFKBIA has the Capacity to Serve as a Diagnostic Biomarker for Prostate Cancer Patient

Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

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