Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma

Gousias, Konstantinos; Theocharous, Theocharis; Simon, Matthias

doi:10.3390/biomedicines10030564

Cited by 42 publications

(21 citation statements)

References 123 publications

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“…In this study, we constructed a novel prognostic model based on necroptosis-associated genes KPNA2, SLC1A5, and RAMP3. KPNA2 ( 26 ), a nuclear import factor, functions as an oncogene in cervical squamous cell carcinoma ( 27 ) and nasopharyngeal carcinoma ( 28 , 29 ). In addition, SLC1A5 acts as a high-affinity transporter of L-glutamine to enhance the growth of epithelial and tumor cells in culture ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Bao

et al. 2022

Front. Immunol.

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BackgroundHepatocellular carcinoma remains the third most common cause of cancer-related deaths worldwide. Although great achievements have been made in resection, chemical therapies and immunotherapies, the pathogenesis and mechanism of HCC initiation and progression still need further exploration. Necroptosis genes have been reported to play an important role in HCC malignant activities, thus it is of great importance to comprehensively explore necroptosis-associated genes in HCC.MethodsWe chose the LIHC cohort from the TCGA, ICGC and GEO databases for this study. ConsensusClusterPlus was adopted to identify the necroptosis genes-based clusters, and LASSO cox regression was applied to construct the prognostic model based on necroptosis signatures. The GSEA and CIBERSORT algorithms were applied to evaluate the immune cell infiltration level. QPCR was also applied in this study to evaluate the expression level of genes in HCC.ResultsWe identified three clusters, C1, C2 and C3. Compared with C2 and C3, the C1 cluster had the shortest overall survival time and highest immune score. The C1 was samples were significantly enriched in cell cycle pathways, some tumor epithelial-mesenchymal transition related signaling pathways, among others. The DEGs between the 3 clusters showed that C1 was enriched in cell cycle, DNA replication, cellular senescence, and p53 signaling pathways. The LASSO cox regression identified KPNA2, SLC1A5 and RAMP3 as prognostic model hub genes. The high risk-score subgroup had an elevated expression level of immune checkpoint genes and a higher TIDE score, which suggested that the high risk-score subgroup had a lower efficiency of immunotherapies. We also validated that the necroptosis signatures-based risk-score model had powerful prognosis prediction ability.ConclusionBased on necroptosis-related genes, we classified patients into 3 clusters, among which C1 had significantly shorter overall survival times. The proposed necroptosis signatures-based prognosis prediction model provides a novel approach in HCC survival prediction and clinical evaluation.

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Section: Discussionmentioning

confidence: 99%

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Bao

et al. 2022

Front. Immunol.

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“…It was later found that RB inactivation occurs in many tumor types, especially in hepatocellular carcinoma, lung cancer, and glioblastoma. [38][39][40] Recently, RB has been shown to play other important roles, such as regulating apoptosis, cell differentiation and angiogenesis, induction and maintenance of senescence, and regulation of invasion and metastasis. 41,42 P21 was the first gene identified to be induced by the wild-type p53 | 11 of 14 their effects on cell cycle progression and survival by controlling the cell cycle, and inducing apoptosis and senescence.…”

Section: Discussionmentioning

confidence: 99%

“…RB was the first identified tumor suppressor, and its encoded protein negatively regulates the cell cycle. It was later found that RB inactivation occurs in many tumor types, especially in hepatocellular carcinoma, lung cancer, and glioblastoma 38–40 . Recently, RB has been shown to play other important roles, such as regulating apoptosis, cell differentiation and angiogenesis, induction and maintenance of senescence, and regulation of invasion and metastasis 41,42 .…”

Section: Discussionmentioning

confidence: 99%

Epstein‐Barr virus miR‐BART2‐5p and miR‐BART11‐5p regulate cell proliferation, apoptosis, and migration by targeting RB and p21 in gastric carcinoma

Zhao

Zhang

et al. 2022

Journal of Medical Virology

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Epstein‐Barr virus (EBV) was the first tumor virus discovered in humans and can cause various types of tumors. Molecular classification suggests that EBV‐associated gastric cancer (EBVaGC) is a unique subtype of gastric cancer.EBV was also the first virus found to encode its own microRNAs. However, the functions of many miRNAs remain unknown. This study investigated the roles and targets of miR‐BART2‐5p (BART2‐5p) and miR‐BART11‐5p (BART11‐5p) in EBVaGC. The expression of RB and p21 in EBVaGC and EBV negative GC (EBVnGC) cells was evaluated by western blotting. Expression of BART2‐5p and BART11‐5p in EBVaGC cells was evaluated by droplet digital PCR. The effects of BART2‐5p or BART11‐5p and their potential mechanisms were further investigated using cell counting kit‐8, colony formation assay, flow cytometry analysis, and transwell assay. BART2‐5p and BART11‐5p were abundantly expressed and RB and p21 were downregulated in EBVaGC cells. BART2‐5p regulates RB and p21 expression by directly targeting them. BART11‐5p regulates RB expression by directly targeting RB. Both BART2‐5p and BART11‐5p promoted proliferation and migration of gastric cancer cells, while inhibiting apoptosis and promoting S‐phase arrest of the cell cycle. Thus, BART2‐5p and BART11‐5p play important roles in promoting proliferation and migration, and inhibiting apoptosis in EBVaGC by targeting RB and p21, thus providing new potential therapeutic targets for EBVaGC.

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“…Cytotoxic agents kill tumor cells by activating the mechanism of apoptosis. Instead, defects in apoptosis signaling pathways contribute to tumor resistance [ 70 ]. Many natural agents have been shown to induce the apoptotic pathway in cancer both in vitro and in vivo [ 71 ].…”

Section: Signaling Molecules and Biological Pathways Targeted By Plan...mentioning

confidence: 99%

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy

Sevastre

Manea

Popescu

et al. 2022

IJMS

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Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating the natural production environment, ongoing studies are currently setting various strategies to significantly manipulate the quantity of anticancer molecules in plants. This review focuses on the recently studied secondary metabolite agents that have shown promising anticancer activity, outlining their potential mechanisms of action and pathways.

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Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma

Cited by 42 publications

References 123 publications

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma

Epstein‐Barr virus miR‐BART2‐5p and miR‐BART11‐5p regulate cell proliferation, apoptosis, and migration by targeting RB and p21 in gastric carcinoma

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy

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