Transcription factors in glioblastoma – Molecular pathogenesis and clinical implications

Papavassiliou, Kostas A.; Papavassiliou, Athanasios G.

doi:10.1016/j.bbcan.2021.188667

Cited by 11 publications

(3 citation statements)

References 98 publications

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“…Transcription factors (TFs) play critical roles in the transcriptional processes that control gene expression; dysregulation of muted TFs is prevalent in glioma and can lead to the development of tumor-related characteristics. Various expressed TFs and their downstream targets in glioma could be utilized for therapeutic goals [ 11 ]. FOX proteins are a broad group of transcription factors that play key roles in a variety of cellular mechanisms, including cellular growth, cell differentiation, proliferation, and cell cycle control.…”

Section: Introductionmentioning

confidence: 99%

Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Tabnak,

Hasanzade Bashkandi,

Ebrahimnezhad

et al. 2023

Cancer Cell Int

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Glioma is the most aggressive and malignant type of primary brain tumor, comprises the majority of central nervous system deaths, and is categorized into different subgroups according to its histological characteristics, including astrocytomas, oligodendrogliomas, glioblastoma multiforme (GBM), and mixed tumors. The forkhead box (FOX) transcription factors comprise a collection of proteins that play various roles in numerous complex molecular cascades and have been discovered to be differentially expressed in distinct glioma subtypes. FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma. Although recent studies considered FOXO subgroups as tumor suppressors, there are pieces of evidence that they may have an oncogenic role. This review will discuss the subtle functions of FOXOs and FOXM1 in gliomas, dissecting their regulatory network with other proteins, microRNAs and their role in glioma progression, including stem cell differentiation and therapy resistance/sensitivity, alongside highlighting recent pharmacological progress for modulating their expression.

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Section: Introductionmentioning

confidence: 99%

Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Tabnak,

Hasanzade Bashkandi,

Ebrahimnezhad

et al. 2023

Cancer Cell Int

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“…Although surgery combined with radio/chemotherapy has remarkably improved quality of life, the prognosis of patients with glioma remains poor [ 8 ]. For glioblastoma (GBM), a World Health Organization (WHO) grade IV glioma, the median survival period is still short (12 ~ 15 months) with a 5-year survival rate of only 4.7% [ 9 ]. The reasons for poor prognosis are the rapid growth of the tumor tissue, extensive infiltration into the adjacent brain tissue, further induction of pseudonecrosis, abundant angiogenesis, and the absence of a therapeutic target [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma

Tan,

Wei,

et al. 2023

BMC Cancer

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Background Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. Methods RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. Results Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. Conclusion Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.

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“…The major complication in treating GBM patients lies in the heterogeneity of the origin of the tumor [2][3][4]. Alterations in many signaling molecules, transcription factors (TFs), co-factors, and epigenetic modifying molecules have been implicated in the pathogenesis of GBM [5][6][7][8][9]. The rapid progression and invasive properties of GBM make it very hard to treat GBM patients.…”

Section: Introductionmentioning

confidence: 99%

JAK3 Inhibition Regulates Stemness and Thereby Controls Glioblastoma Pathogenesis

Smedley,

Patra

2023

Cells

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Glioblastoma multiforme (GBM) is the most deadly brain tumor, effective treatment options for which still remain elusive. The current treatment procedure of maximal resection followed by chemotherapy has proved to be grossly insufficient to prevent disease progression and death. Despite best efforts, the maximum survival post-diagnosis is a mere 1.5 years. Therefore, there is a huge unmet clinical need to find effective therapeutic procedures to prevent the pathogenesis and relapse of GBM. Small-molecule inhibitors of signaling pathways are an attractive option to prevent various types of tumors. However, no effective small-molecule inhibitors have been successful against GBM in clinical trials. Various signaling pathways are altered and an array of signaling molecules, transcription factors (TFs), and epigenetic modifying factors have been implicated in the pathogenesis of GBM. JAK-STAT pathway alteration is an important contributor to GBM pathogenesis and relapse. Many small-molecule inhibitors of JAKs, or STAT TFs, especially JAK2 and STAT3, have been assessed for their anti-tumor activity in GBM. However, no definitive success so far has been achieved. Herein, by using two small-molecule inhibitors of JAK3, we show that they are quite effective in inhibiting GBM cell proliferation and neurosphere formation, downregulating their stemness character, and inducing differentiation into neuronal origin cells. The effect of a single treatment with the drugs, both in a serum-containing differentiation medium and in a proliferation medium containing EGF and FGF, was really strong in limiting GBM cell growth, suggesting a potential therapeutic application for these JAK inhibitors in GBM therapy.

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Transcription factors in glioblastoma – Molecular pathogenesis and clinical implications

Cited by 11 publications

References 98 publications

Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics

Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma

JAK3 Inhibition Regulates Stemness and Thereby Controls Glioblastoma Pathogenesis

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