Silencing Aurora-kinase-A (AURKA) reinforced the sensitivity of diffuse large B-cell lymphoma cells to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) via suppressing β-Catenin and RAS-extracellular signal-regulated protein kinase (ERK1/2) pathway

Wang, Shaoxiong; Sun, Li

doi:10.1080/21655979.2021.1985346

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…High expression of AURKA has been reported in various tumors ( Yan et al, 2016 ; Wu et al, 2018 ; Wang-Bishop et al, 2019 ; Yi et al, 2021 ). Most notably, studies have explored the biological function of AURKA in human cancers, such as diffuse large B-cell lymphoma, glioblastoma, gastric, cervical, colorectal, and liver cancers ( Shen et al, 2019 ; Liu et al, 2021 ; Mesquita et al, 2021 ; Nguyen et al, 2021 ; Wang and Sun, 2021 ; Wu et al, 2021 ). In addition, inhibition of AURKA was shown to result in a significant reduction of GPX4 and induction of ferroptosis in tumor cells ( Gomaa et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

et al. 2022

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This study comprehensively explored the clinical function of Aurora kinase A (AURKA) gene in nasopharyngeal carcinoma (NPC) and analyzed its potential as a therapeutic target in cancer. Data were downloaded from GEO, STRING, GTEx, and CellMiner databases, and subjected to multiple bioinformatic analyses, including differential expression analysis, WCGNA, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), miRNA-hub gene regulatory network analysis, immune cell infiltration, and drug sensitivity analysis. In-depth analysis of AURKA gene expression in NPC and its corresponding clinicopathological features was performed to explore its potential as a therapeutic target. Moreover, AURKA gene expression in NPC was validated by qRT-PCR in 21 NPC tissues and 17 normal nasopharyngeal epithelial tissues. AURKA was highly expressed in NPC tissues. Enrichment analysis of AURKA and its co-expressed hub genes indicated their oncogenic role in NPC and their potential involvement in cancer-promoting processes through histone kinase activity and microtubule motility activity, cell cycle, and p53 signaling pathways. AURKA high expression group had greater infiltration of neutrophils, macrophages M2, and dendritic cells resting and less infiltration of T cells CD4+ naïve and T cells γδ. Drug susceptibility analysis found that dacarbazine, R-306465, vorinostat, and other antitumor drugs that act on the cell cycle were closely related to AURKA. qRT-PCR verified the high expression of AURKA in NPC tissues (p < 0.05). We confirmed upregulation of AURKA in NPC tissues. Our results support an oncogenic role of AURKA in the context of NPC, and indicate its potential role as a novel therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

et al. 2022

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“…AURKA inhibitor has presented preclinical synergy effects on the immunochemotherapy of DLBCL with rituximab and vincristine. At the same time, silencing AURKA reinforces the sensitivity of DLBCL neoplastic cells to CHOP by inhibiting β-catenin and the RAS-ERK1/2 pathway [70,77] .…”

Section: Discussionmentioning

confidence: 95%

“…Indeed, the up-regulation of AURKA in several malignancies patients is related to a poorer prognosis. Furthermore, high expression of AURKA also induces the mutation of the tumor suppressors like p21, p53, or retinoblastoma and the activation of the oncogenic factors like c-MYC, NF-kB, or β-Catenin as well as the deregulation of multiple cancer-related signaling pathways like TP53, mTOR, Hippo, PI3K-Akt, WNT, ERK1/2 alongside with FOXO and Ras-MAPK as well as NF-κB genes through stopping apoptosis and enhancing cancer cell proliferation, cell survival, genomic instability, epithelial-mesenchymal transition, metastasis, self-renewal of cancer stem cells, plasticity, chemo/drug-resistance, oncogenic transformation, cancer stem cell phenotype, and inhibiting cancer cell apoptosis, promoting tumorigenesis and progression [66][67][68][69][70][71][72][73][74][75][76] . Moreover, in relapsed/refractory aggressive B-cell Lymphoma, patients with overexpression and/or ampli cation of AURKA related to tumor progression and poor patient outcomes [78] .…”

Section: Discussionmentioning

confidence: 99%

Identification of the driving mechanisms associated with aggressive transformation and prognosis in follicular lymphomas

Wang

Chen

et al. 2022

Preprint

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Follicular lymphoma (FL) is the most frequently common indolent subtype of non-Hodgkin’s lymphoma (NHL), with a generally favorable prognosis. Recent studies have elucidated a subset of patients undergoing histological transformations (HTs) into transformed follicular lymphoma (tFL) and diffuse large B-cell lymphoma (DLBCL) aggressive morphology, leading to a poorer prognosis. Investigating the mechanisms of oncogenic transformation further could be helpful to find potential prognostic biomolecular markers that could be used to develop new treatment strategies or combination strategies. In this study, we conducted integrative bioinformatics analyses of the GEO, DAVID, STRING, GeneMANIA, TRRUST, and DGIdb database to determine which hub genes contributed to aggressive HTs of FL. The results show that HTs-related 462 and 503 differential genes contained between tFL and FL as well as between DLBCL and FL, respectively. Further functional enrichment analysis of these differential genes showed that the common significant enrichment in cell division, immune response, mitotic spindle organization, chromosome segregation of biological processes (BPs), extracellular space, extracellular region, and external side of the plasma membrane of cellular components (CCs), protein binding, microtubule-binding, heparin-binding, extracellular matrix structural constituent, and integrin binding of molecular functions (MFs), and cytokine-cytokine receptor interaction, chemokine signaling pathway, and viral protein interaction with cytokine and cytokine receptor signaling pathway of KEGG pathways. Subsequently, construct an overlapping PPI network to screen 10 hub genes (CCNB1, AURKA, RRM2, CDK1, BUB1B, CDC6, ASPM, TTK, TPX2, and NCAPG). We then analyzed the transcription factor regulation and drug regulatory networks. In summary, our study identified 3 oncogenic transformation molecules (CDK1, RRM2, and AURKA) as important biomarkers in the progression of FL. Their abnormal expression is closely associated with prognosis and sensitivity to standard therapy and can help us better understand the aggressive HTs of FL.

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“…In addition, the genome of DLBCL is altered by chromosomal translocations and aberrant somatic hypermutation, both of which are intimately connected to the physiologic IG DNA remodeling processes operating in B lymphocytes (Pasqualucci and Dalla-Favera, 2018). Among them, the canonical cancer-related RAS/RAF/MEK/ERK pathway is considered to be associated with DLBCL cell proliferation, migration, invasion, drug sensitivity, and prognosis (Jiang et al, 2018;Yang et al, 2020;Sun et al, 2021;Wang and Sun, 2021).…”

Section: Introductionmentioning

confidence: 99%

RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma

Liang

Liu

et al. 2022

Front. Pharmacol.

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Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis.Methods: RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein–protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database.Results: RAB39B was highly expressed in multiple tumors including DLBCL. The protein–protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine–cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4+ T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. In vitro experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells.Conclusion: RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.

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Silencing Aurora-kinase-A (AURKA) reinforced the sensitivity of diffuse large B-cell lymphoma cells to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) via suppressing β-Catenin and RAS-extracellular signal-regulated protein kinase (ERK1/2) pathway

Cited by 5 publications

References 49 publications

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

Identification of the driving mechanisms associated with aggressive transformation and prognosis in follicular lymphomas

RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma

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