The role of HOPX in normal tissues and tumor progression

Liu, Yijun; Zhang, Wenling

doi:10.1042/bsr20191953

Cited by 26 publications

(35 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, unsupervised hierarchical clustering analysis identified an expression pattern in line with the G007-LK sensitivity; the most sensitive cultures (T0965 and T1008) clustered apart from the least sensitive cultures (T1023 and T2609; Figure S1a). The least sensitive cultures displayed significantly higher expression of genes related to GBM progression and GSC proliferation and stemness, including SPARCL1, HOPX, ID1, ID3, CPE and CXRC4 (Table S1) [36][37][38][39]. However, when analyzing the cultures based on GSC subtypes [40,41], they all displayed a proneural rather than a mesenchymal signature ( Figure S1b).…”

Section: Global Gene Expression Analysis Reveals That Gsc Cultures CLmentioning

confidence: 99%

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

Kierulf-Vieira

Sandberg

Waaler

et al. 2020

Cancers

View full text Add to dashboard Cite

Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. Four primary GSC cultures and two primary adult neural stem cell cultures were treated with G007-LK and subsequently evaluated through the measurement of growth characteristics, as well as the expression of WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Treatment with G007-LK decreased in vitro proliferation and sphere formation in all four primary GSC cultures in a dose-dependent manner. G007-LK treatment altered the expression of key downstream WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Finally, cotreatment with the established GBM chemotherapeutic compound temozolomide (TMZ) led to an additive reduction in sphere formation, suggesting that WNT/β-catenin signaling may contribute to TMZ resistance. These observations suggest that tankyrase inhibition may serve as a supplement to current GBM therapy, although more work is needed to determine the exact downstream mechanisms involved.

show abstract

Section: Global Gene Expression Analysis Reveals That Gsc Cultures CLmentioning

confidence: 99%

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

Kierulf-Vieira

Sandberg

Waaler

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Loss of ANTXR1 results in endothelial basement membrane loss and leaky blood vessels HOPX 37 Hop homeodomain protein, cofactor Acts via serum response factor (SRF), modulating the expression of cardiac genes and stress-induced cardiac hypertrophy MCUB 38 Mitochondrial calcium uniporter Role in cardiac homeostasis, response to cardiac stress including ischemia PIGX 39 Phosphatidylinositol glycan anchor biosynthesis class X Associated with hypertension. Forms a complex with PIG-M that regulates several processes, including maintenance of arterial blood pressure.…”

Section: Genesmentioning

confidence: 99%

Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

Taylor¹,

Das²,

Pearson³

et al. 2020

Preprint

View full text Add to dashboard Cite

BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease, hypertension and type 2 diabetes mellitus. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis, selecting controls who had not developed sepsis despite having maximum co-morbidity risk and exposure to sepsis-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

show abstract

“…The B-cell population was also found to depict the prolonged the high response with an average of 472 cells per mm 3 to a long time and further helped to evoke memory cells to strengthen immunity against the re-infection by memorizing the immune system. Besides, we found it to stimulate the helper T-cells up to a maximum level of 1394 cells per mm 3 with an average elevation of 1373 cells per mm 3 , along with other potential immune response generator regulators, including the interferons, natural killer cells, and interleukins. Obtained results depicted the potency of designed antigenic determinant to elicit a robust immune response against the tumorigenic state.…”

Section: Immune Response Simulation Analysismentioning

confidence: 87%

“…Administration of antigenic determinant elicited the high titer of primary antibodies (IgM, IgG1, IgG2) in the early days and then slowly decreased till 30 days. Importantly, it showed the elicitation of cytotoxic T-cells up to the maximum 1125 cells per mm 3 with an average optimal level elevation of 1102 cells per mm 3 ;…”

Section: Immune Response Simulation Analysismentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxic T-lymphocyte elicited therapeutic vaccine candidate targeting cancer against MAGE-A11 carcinogenic protein

et al. 2020

View full text Add to dashboard Cite

Immunotherapy is a breakthrough approach for cancer treatment and prevention. By exploiting the fact that cancer cells have overexpression of tumor antigens responsible for its growth and progression, which can be identified and removed by boosting the immune system. In silico techniques have provided efficient ways for developing preventive measures to ward off cancer. Herein, we have designed a potent cytotoxic T-lymphocyte epitope to elicit a desirable immune response against carcinogenic melanoma-associated antigen-A11. Potent epitope was predicted using reliable algorithms and characterized by advanced computational avenue CABS molecular dynamics simulation, for full flexible binding with HLA-A*0201 and androgen receptor to large-scale rearrangements of the complex system. Results showed the potent immunogenic construct (KIIDLVHLL), from top epitopes using five algorithms. Molecular docking analyses showed the strong binding of epitope with HLA-A*0201 and androgen receptor with docking score of -780.6 and -641.06 kcal/mol, respectively. Molecular dynamics simulation analysis revealed strong binding of lead epitope with androgen receptor by involvement of 127 elements through atomic-model study. Full flexibility study showed stable binding of epitope with an average RMSD 2.21 Å and maximum RMSD value of 6.48 Å in optimal cluster density area. The epitope also showed remarkable results with radius of gyration 23.0777 Å, world population coverage of 39.08% by immune epitope database, and TAP affinity IC50 value of 2039.65 nm. Moreover, in silico cloning approach confirmed the expression and translation capacity of the construct within a suitable expression vector. This study paves way for a potential immunogenic construct for prevention of cancer.

show abstract

The role of HOPX in normal tissues and tumor progression

Cited by 26 publications

References 75 publications

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

Cytotoxic T-lymphocyte elicited therapeutic vaccine candidate targeting cancer against MAGE-A11 carcinogenic protein

Contact Info

Product

Resources

About