scholarly journals MUC14-Related ncRNA-mRNA Network in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1677
Author(s):  
Shuqian Wang ◽  
Jing Jin ◽  
Jing Chen ◽  
Weiyang Lou
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Comprehensive Analysis ◽  
Action Mechanism ◽  
Protein Levels ◽  
Molecular Action ◽  
Study Results ◽  
In Silico Analyses ◽  
Comprehensive Study

Growing evidences have showed that mucins (MUCs) are linked to occurrence and progression of human cancers. However, a comprehensive study regarding the expression, diagnosis, prognosis and mechanism of MUCs in breast cancer remains absent. Methods: A series of in silico analyses were employed in this study. Results: After performing comprehensive analysis for MUCs, MUC14 was identified as the most potential regulator in breast cancer, with downregulated expression in both mRNA and protein levels and significant diagnostic and prognostic values in breast cancer. Mechanistic exploration revealed that a potential ncRNA-mRNA axis, involving LINC01128/LINC01140/SGMS1-AS1/LINC00667-miR-137/miR-429-BCL2, might be partially responsible for MUC14′s functions in breast cancer. Conclusions: Collectively, our study elucidated a key role of MUC14 in breast cancer and also provided some clues for explanation of the molecular action mechanism of MUC14 in breast cancer.

scholarly journals The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt-FoxO1 pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Junsheng He ◽  
Ailiang Zhang ◽  
Zhiwen Song ◽  
Shiwu Guo ◽  
Yuwei Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Sublethal Concentration ◽  
Action Mechanism ◽  
Protein Levels ◽  
Signaling Axis ◽  
Silent Information Regulator 1

Abstract Objective: The senescence of nucleus pulposus (NP) cells induced by oxidative stress is one of the important causes of intervertebral disc degeneration (IDD). Herein, we investigated the role and action mechanism of silent information regulator 1 (SIRT1) in oxidative stress-induced senescence of rat NP cell. Methods: Premature senescence of rat NP cells was induced by sublethal concentration of hydrogen peroxide (H2O2) (100 μM). SIRT1 was activated with SRT1720 (5 μM) to explore its effect on NP cells senescence. FoxO1 and Akt were inhibited by AS1842856 (0.2 μM) and MK-2206 (5 μM), respectively, to explore the role of Akt-FoxO1-SIRT1 axis in rat NP cells. Pretreatment with the resveratrol (20 μM), a common antioxidant and indirect activator of SIRT1, was done to investigate its role in senescent rat NP cells. Results: The mRNA and protein levels of SIRT1 were decreased in H2O2-induced senescent rat NP cells, and that specific activation of SIRT1 suppresses senescence. And the Akt-FoxO1 pathway, as the upstream of SIRT1, might be involved in the regulation of H2O2-induced senescence of rat NP cells by affecting the expression of SIRT1. In addition, the resveratrol played an anti-senescence role in rat NP cells, which might affect the Akt-FoxO1-SIRT1 axis. Conclusion: SIRT1 ameliorated oxidative stress-induced senescence of rat NP cell which was regulated by Akt-FoxO1 pathway, and resveratrol exerted anti-senescence effects by affecting this signaling axis.

scholarly journals In silico analyses identify gene-sets, associated with clinical outcome in ovarian cancer: role of mitotic kinases

Oncotarget ◽  
2016 ◽  
Vol 7 (16) ◽  
pp. 22865-22872 ◽  
Author(s):  
Alberto Ocaña ◽  
Javier Pérez-Peña ◽  
Ana Alcaraz-Sanabria ◽  
Verónica Sánchez-Corrales ◽  
Cristina Nieto-Jiménez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
In Silico ◽  
Mitotic Kinases ◽  
Gene Sets ◽  
In Silico Analyses

scholarly journals Highlighting the Role of Cdk6 Associated MicroRNAs in Cancer Treatment Using In Silico Approaches

2020 ◽  
pp. 1-14
Author(s):  
Sidra Batool ◽  
Muhammad Sibte Hasan Mahmood ◽  
Tiyyaba Furqan ◽  
Sidra Batool
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
In Silico ◽  
Drug Target ◽  
In Silico Analysis ◽  
Kinase Domain ◽  
Protein Kinase Domain ◽  
Over Expression ◽  
Silico Analysis

MicroRNAs (miRNAs) are small non-coding RNA’s that controls the regulation of a gene. Due to the over expression or under expression of miRNAs it leads to cause tumor or any other type of cancers such as, melanoma, lymphoma, cardiovascular issue, breast cancer etc. So, miRNAs can be used as a drug target for cancer therapy. This study aimed to check binding cavities of microRNA's involved in regulation of CDK6 protein. There are 23 different families of miRNAs that are involved in regulation of CDK6. Each family has one or more miRNAs. All these miRNAs are involved in the up regulation or downregulation of a gene, which lead to different type of cancers. All miRNAs of each family docked with mRNA CDK6 protein. After performing in silico analysis of binding interactions of mRNA with miRNAs the results were further refined by their comparison with information regarding their energies, interaction of the mRNA and miRNAs. The results show that all miRNAs lie in Protein Kinase domain, but the residues that lie is different within the families and across the families.

scholarly journals The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter semiSWEET

2020 ◽  
Author(s):  
Sunil Thomas
Keyword(s):  
In Silico ◽  
Transmembrane Domain ◽  
Sugar Transport ◽  
Protein S ◽  
M Protein ◽  
Sugar Transporter ◽  
Structural Protein ◽  
And Function ◽  
In Silico Analyses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. The advantage and role of sugar transporter like structures in viruses are unknown. If they are involved in energy metabolism, they may aid in the rapid proliferation and replication of the virus. Biological experiments should be performed to validate the presence and function of the semiSWEET sugar transporter.

Abstract 18789: BRCA2 is a Novel Regulator of Endothelial Cell Function and Apoptosis Following Hyperglycemia

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Pratiek N Matkar ◽  
Mohammed Al-Omran ◽  
Subodh Verma ◽  
Howard Leong-Poi ◽  
Krishna K Singh
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Endothelial Dysfunction ◽  
Brca2 Mutation ◽  
No Production ◽  
Ros Production ◽  
Endothelial Cell Function ◽  
Protein Levels ◽  
Mutation Carriers

Background: Germ-line mutations in the tumor suppressor gene BRCA2 (breast cancer 2, early onset) predispose carriers mostly to breast cancer, and BRCA2 mutation carriers also face a 2-fold increase in the risk of developing diabetes.Hyperglycemia, the hallmark of diabetes, is a major risk factor for endothelial dysfunction leading to vascular complications. The relationship linking role of BRCA2 in the development of diabetes and endothelial dysfunction remains mainly unexplored. Methods: To elucidate the role of BRCA2 in diabetes and endothelial apoptosis/dysfunction in vitro, we silenced BRCA2 in human umbilical vein endothelial cells (ECs) and evaluated the markers of EC function and apoptosis following hyperglycemia. Results: We first confirmed the basal expression of BRCA2 in ECs at transcript and protein levels by qPCR and immunoblotting, respectively. Interestingly, hyperglycemia significantly induced BRCA2 expression after 48 hours of treatment. We then silenced BRCA2 in ECs and confirmed successful silencing at transcript and protein levels. Hyperglycemia significantly increased the reactive oxygen species (ROS) production in the BRCA2-deficient ECs in comparison to control ECs. Increased ROS production was associated with exacerbated DNA-damage in BRCA2-silenced ECs as evidenced by increased expression and activation of DNA double-stranded breaks (DSBs) marker H2A.X and reduced RAD51-foci formation, an essential regulator of DSB repair. Increased DSBs were associated with significantly increased activation of p53. Elevated levels of DNA-damage and activated-p53 were further associated with significantly increased hyperglycemia-induced apoptosis in BRCA2-silenced ECs as measured by immunoblotting for cleaved-caspase-3, Bax and by TUNEL-staining.Key indices of endothelial function, including tube formation and NO production, were significantly reduced following hyperglycemia-treatment in BRCA2-deficient ECs. Conclusion: Our data for the first time, show an entirely novel role of BRCA2 as a regulator of endothelium in the setting of hyperglycemia, and provide important clues regarding the potential susceptibility of BRCA2 mutation carriers to hyperglycemia-induced cardiovascular complications.

Abstract 18705: BRCA2 is a Novel Regulator of Endothelial Cell Function and Apoptosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Pratiek N Matkar ◽  
Wei J Cao ◽  
Mohammed Al-Omran ◽  
Subodh Verma ◽  
Howard Leong-Poi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
Dna Damage Repair ◽  
Genotoxic Stress ◽  
Tube Formation ◽  
Protein Levels ◽  
Damage Repair

Background: Germ-line mutations in the tumor suppressor gene BRCA2 (breast cancer 2, early onset) predispose carriers not only to breast cancer, but also to other cancers. BRCA2 plays crucial role in the genome integrity maintenance and is central to DNA-damage repair. BRCA2-associated DNA-damage responses are not only specific to cancer syndromes but also represent a common pathophysiological basis for diverse cardiovascular diseases (CVDs). These observations led us to hypothesize that BRCA2 is an essential regulator of endothelial function and apoptosis following genotoxic stress. Methods: To elucidate the role of BRCA2 in endothelial cells, we silenced BRCA2 in the human umbilical vein endothelial cells (ECs) and measured the indices of EC function; tube formation and proliferation, DNA-damage/repair and apoptosis by qPCR, immunoblotting and immunofluorescence following doxorubicin (Dox) treatment. Results: We confirmed the basal expression and successful silencing of BRCA2 in ECs at transcript and protein levels by qPCR and immunoblotting, respectively. Genotoxic stress in the form of Dox exacerbated DNA-damage in BRCA2-silenced ECs as evident by increased expression and activation of DNA double-stranded breaks (DSBs) marker H2A.X and reduced RAD51-foci formation, an essential regulator of DSB repair. Increased DSBs were associated with significantly increased expression and activation of p53, and increased expression of p53-upregulated modulator of apoptosis PUMA. Elevated levels of DNA-damage and p53 were further associated with significantly increased Dox-induced apoptosis in BRCA2-silenced ECs as measured by immunoblotting for cleaved-caspase-3 and TUNEL-staining.Key indices of endothelial function, including tube formation and proliferation, were significantly reduced following Dox-treatment in BRCA2-deficient ECs, which was accompanied with significantly increased expression of cell cycle inhibitor, p21 at transcript and protein levels. Conclusion: Our data for the first time, show an entirely novel role of BRCA2 as a regulator of endothelium, and provide important clues regarding a potential susceptibility of BRCA2 mutation carriers to anthracycline-induced CVDs, a cornerstone of chemotherapy for cancer.

scholarly journals Model-based in silico analysis of the PI3K/Akt pathway: the elucidation of cross-talk between diabetes and breast cancer

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5917 ◽  
Author(s):  
Sammia Rehman ◽  
Ayesha Obaid ◽  
Anam Naz ◽  
Amjad Ali ◽  
Shahzina Kanwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Insulin Signaling ◽  
In Silico ◽  
In Silico Analysis ◽  
Positive Association ◽  
Pi3k Pathway ◽  
Diabetic Patients ◽  
Breast Cancer Patients

Background A positive association between diabetes and breast cancer has been identified by various epidemiological and clinical studies. However, the possible molecular interactions between the two heterogeneous diseases have not been fully determined yet. There are several underlying mechanisms which may increase the risk of breast cancer in diabetic patients. Introduction In this study, we focused on the role of O-GlcNAc transferase (OGT) enzyme in the regulation of phosphatidylinositol-3 kinase (PI3K) pathway through activation/deactivation of Akt protein. The efficiency of insulin signaling in adipocytes is reduced as a result of OGT overexpression which further attenuates Akt signaling; as a result, the efficiency of insulin signaling is reduced by downregulation of insulin-responsive genes. On the other hand, increased expression of OGT results in Akt activation in breast cancer cells, leading to enhanced cell proliferation and inhibition of the apoptosis. However, the interplay amongst these signaling pathways is still under investigation. Methods In this study, we used Petri nets (PNs) to model and investigate the role of PI3K and OGT pathways, acting as key players in crosstalk between diabetes and breast cancer, resulting in progression of these chronic diseases. Moreover, in silico perturbation experiments were applied on the model to analyze the effects of anti-cancer agents (shRNA and BZX) and anti-diabetic drug (Metformin) on the system. Results Our PN model reflects the alterations in protein expression and behavior and the correlation between breast cancer and diabetes. The analysis proposed two combination therapies to combat breast cancer progression in diabetic patients including combination of OGTmRNA silencing and OGT inhibitor (BZX) as first combination and BZX and Metformin as the second. Conclusion The PN model verified that alterations in O-GlcNAc signaling affect both insulin resistance and breast cancer. Moreover, the combination therapy for breast cancer patients consisting of anti-diabetic drugs such as Metformin along with OGT inhibitors, for example BZX, can produce better treatment regimens.

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