Analysis of MCM Proteins’ Role as a Potential Target of Statins in Patients with Acute Type A Aortic Dissection through Bioinformatics

Liang, Zheyong; Zhang, Yongjian; Chen, Qiang; Hao, Jiejie; Wang, Haichen; Li, Yongxin; Yang, Yan

doi:10.3390/genes12030387

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…First, the study did not examine whether the relationship of GC with the molecules was direct or indirect; hence, future research is required. Second, in terms of potential therapeutic targets, MCM4, MCM2, and MCM10 play an important role in aortic dissection, and MCMs expression is inhibited by statin treatment [29]. Therefore, MCM4 inhibition acting as a tumor suppressor could become a new therapeutic target through drug repositioning.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

Katsuya¹,

Ishikawa²,

Kido³

et al. 2022

Pathobiology

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Introduction: Gastric cancer (GC) is a leading cause of cancer-related death worldwide. This study focused on minichromosome maintenance 4 (MCM4), a DNA helicase component that functions in DNA replication. Using spheroid colony formation, having a colony rich in cancer stem cells, this study aimed to investigate the clinicopathological importance of MCM4. Methods: We examined MCM4 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analysis in 10 and 113 GC cases, respectively. MCM4 function in GC was also investigated by RNA interference in GC cell lines. Results: In qRT-PCR and IHC analysis, high MCM4 expression was found in 60% and 83% of GC cases, respectively. MCM4-positive GC cases were significantly associated with higher T grade and tumor stage. Additionally, high MCM4 expression was significantly associated with poor prognosis and was an independent prognostic factor in multivariate analysis. MCM4 was significantly coexpressed with CD133, matrix metalloproteinase 7 (MMP7), epidermal growth factor (EGFR), and mesenchymal-epithelial transition factor (cMET). In GC cell lines, MCM4 knockdown affected cell growth and protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and EGFR pathways. Conclusion: These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.

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Section: Discussion/conclusionmentioning

confidence: 99%

Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

Katsuya¹,

Ishikawa²,

Kido³

et al. 2022

Pathobiology

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“…Statins also reverse the increase in minichromosome maintenance (MCM) proteins in aortic disease. 69 In our cohort, the levels of MCM2, MCM3, MCM4, and MCM5 were diminished in VSMCs from TAA patients with a BAV compared to those with a TAV. Thus, statin therapy may prove to be contraindicated for BAV-TAA patients.…”

Section: Clinical Perspectives For Bav Patientsmentioning

confidence: 48%

“…Statins have been reported to inhibit TAA and dissection through different mechanisms. , Statins can upregulate specific small G proteins that protect against phenotype switching and reduce DNA oxidative damage, potentially providing benefits for BAV-TAA patients. Statins also reverse the increase in minichromosome maintenance (MCM) proteins in aortic disease . In our cohort, the levels of MCM2, MCM3, MCM4, and MCM5 were diminished in VSMCs from TAA patients with a BAV compared to those with a TAV.…”

Section: Discussionmentioning

confidence: 67%

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients

Martin-Blazquez,

Martin-Lorenzo,

Santiago-Hernandez

et al. 2024

J. Proteome Res.

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Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by mass spectrometry. DNA oxidative damage assay and cell cycle profiling were performed in three independent cohorts supporting proteomics data. The alteration of secreted proteins was confirmed in plasma. Stress phenotype, oxidative stress, and enhanced DNA damage response (increased S-phase arrest and apoptosis) were found in BAV-TAA patients. The increased levels of plasma C1QTNF5, LAMA2, THSB3, and FAP confirm the enhanced stress in BAV-TAA. Plasma FAP and BGN point to an increased inflammatory condition in TAV. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA. The molecular pathways identified support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients, showing specific markers in plasma which may serve to monitor therapy efficacy.

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“…It follows that our future focus and effort in the field of AAD research will be integrated studies combining proteomics, metabolomics, and other histological concepts. We anticipate finding more drug-targeting protein families in the future thanks to multi-omics integration approaches, which will allow us to investigate the molecular targets and potential pharmacological action mechanisms on AAD ( 166 ). The future therapy pathway for AAD will also include a critical stage involving the screening of biomarkers for acute pharmacological inhibitors, which may also serve as a model for the construction of drug resistance profiles.…”

Section: Current Shortcomings and Future Prospectsmentioning

confidence: 99%

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

Hao

Cheng

Jiang

et al. 2022

Front. Cardiovasc. Med.

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Acute aortic dissection (AAD) is a cardiovascular disease that manifests suddenly and fatally. Due to the lack of specific early symptoms, many patients with AAD are often overlooked or misdiagnosed, which is undoubtedly catastrophic for patients. The particular pathogenic mechanism of AAD is yet unknown, which makes clinical pharmacological therapy extremely difficult. Therefore, it is necessary and crucial to find and employ unique biomarkers for Acute aortic dissection (AAD) as soon as possible in clinical practice and research. This will aid in the early detection of AAD and give clear guidelines for the creation of focused treatment agents. This goal has been made attainable over the past 20 years by the quick advancement of omics technologies and the development of high-throughput tissue specimen biomarker screening. The primary histology data support and add to one another to create a more thorough and three-dimensional picture of the disease. Based on the introduction of the main histology technologies, in this review, we summarize the current situation and most recent developments in the application of multi-omics technologies to AAD biomarker discovery and emphasize the significance of concentrating on integration concepts for integrating multi-omics data. In this context, we seek to offer fresh concepts and recommendations for fundamental investigation, perspective innovation, and therapeutic development in AAD.

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Analysis of MCM Proteins’ Role as a Potential Target of Statins in Patients with Acute Type A Aortic Dissection through Bioinformatics

Cited by 4 publications

References 39 publications

Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

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