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.

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

scholarly journals Mechanisms of Metastasis and Cell Mobility – The Role of Metabolism

2019 ◽  
Vol 79 (02) ◽  
pp. 184-188 ◽  
Author(s):  
Carsten Gründker ◽  
Matthias Läsche ◽  
Johanna Hellinger ◽  
Günter Emons
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Breast Cancer Patients ◽  
Metastatic Cascade ◽  
Cell Mobility ◽  
Tumour Metastasis ◽  
Multi Stage ◽  
Mesenchymal Transformation

AbstractTumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.

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 Role of Long Noncoding RNAs in Patients With Luminal A Invasive Breast Ductal Carcinoma

2021 ◽  
Author(s):  
Nahal Eshghifar ◽  
Fatemeh Rouhollah ◽  
Nooshin Barikrow ◽  
Farkhondeh Pouresmaeili ◽  
Mohammad Taheri
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Ductal Carcinoma ◽  
Positive Association ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Protein Coding ◽  
Diagnostic Approaches ◽  
Breast Tissues

Abstract Breast cancer is the most common form of cancer in women around the world. The molecular mechanisms of this heterogeneous disease have been extensively investigated; but still; need many sensitive and specific markers for prognostic and early diagnostic approaches. Non-protein coding RNAs known as lncRNAs are reported in tumorogenesis involvement. hence could be used as therapeutic targets.In the present study, we examined the expression levels of CCAT1, PDCD4, PDCD4-AS1, and MEG3 LncRNAs in tumor and adjacent breast tissues in 88 Iranian patients by quantitative real-time PCR. CCAT1 was notably overexpressed and PDCD4-AS1 was decreased in tumor samples, PDCD4 and PDCD4-AS1 showed a positive association with each other, higher levels of PDCD4-AS1 were associated with better survival, tumor samples showed lower levels of PDCD4 compared to normal tissue.Our findings show that lncRNAs play critical roles in controlling post-transcriptional gene expression of key tumor suppressor or oncogenic genes, leading to TNBC progression.As a result, this research looked into the prognostic role of lncRNAs in breast cancer patients.

scholarly journals The Role of PI3K Inhibition in the Treatment of Breast Cancer, Alone or Combined With Immune Checkpoint Inhibitors

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhizhu Zhang ◽  
Ann Richmond
Keyword(s):  
Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Pi3k Pathway ◽  
Breast Cancer Patients ◽  
Current Standard ◽  
Development Of Resistance ◽  
Pi3k Inhibition

Dysregulation of phosphoinositide 3-kinase (PI3K) signaling is highly implicated in tumorigenesis, disease progression, and the development of resistance to the current standard of care treatments in breast cancer patients. This review discusses the role of PI3K pathway in breast cancer and evaluates the clinical development of PI3K inhibitors in both early and metastatic breast cancer settings. Further, this review examines the evidence for the potential synergistic benefit for the combination treatment of PI3K inhibition and immunotherapy in breast cancer treatment.

miR-744/eNOS/NO axis: A novel target to halt triple negative breast cancer progression

2021 ◽  
pp. 1-9
Author(s):  
Farah Hady El Kilany ◽  
Rana Ahmed Youness ◽  
Reem Amr Assal ◽  
Mohamed Zakaria Gad
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
In Silico ◽  
In Silico Analysis ◽  
No Production ◽  
Cellular Viability ◽  
Griess Reagent ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Silico Analysis

BACKGROUND: Nitric oxide (NO) may have a dual role in cancer. At low concentrations, endogenous NO promotes tumor growth and proliferation. However, at very high concentrations, it mediates cancer cell apoptosis and inhibits cancer growth. High levels of NO have been observed in blood of breast cancer (BC) patients, which increases tumor blood flow and promotes angiogenesis. To date, the regulation of NO-synthesizing enzyme, eNOS, by miRNAs has not been adequately investigated in BC. Therefore, the main aim of this study is to unravel the possible regulation of eNOS by miRNAs in BC and to examine their influence on NO production and BC progression. METHODS: Expression profile of eNOS in Egyptian BC patients and MDA-MB-231 cell lines was investigated using qRT-PCR. In-silico analysis was performed to predict a putative upstream regulator of eNOS. miR-744-5p was selected and its expression was quantified in BC tissues using qRT-PCR. MDA-MB-231 cells were cultured and transfected with miR-744-5p using lipofection method. NO levels were determined using Griess Reagent. Cellular viability and colony-forming ability were assessed using MTT and colony-forming assays; respectively. RESULTS: eNOS and miR-744-5p were significantly up-regulated in BC tissues compared to paired normal tissues. In-silico analysis revealed that miR-744-5p putatively binds to eNOS transcript with high binding scores. Transfection of MDA-MB-231 cells with miR-744-5p mimics resulted in a significant up-regulation of eNOS and consequently NO levels. In addition, miR-744-5p transfection led to an increase in cellular viability and colony-forming ability of the MDA-MB-231. CONCLUSION: miR-744-5p acts as an upstream positive regulator of the NO synthesizing enzyme, eNOS which in turn elevates NO levels. Furthermore, miR-744-5p is a novel oncogenic miRNA in BC. Thus, targeting miR-744/eNOS/NO axis may act as a therapeutic tool in TNBC.

scholarly journals In Vitro and in Silico Analysis of miR-125a with rs12976445 Polymorphism in Breast Cancer Patients

2020 ◽  
Vol 10 (20) ◽  
pp. 7275
Author(s):  
Tomasz P. Lehmann ◽  
Joanna Miskiewicz ◽  
Natalia Szostak ◽  
Marta Szachniuk ◽  
Sylwia Grodecka-Gazdecka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
In Silico ◽  
Growth Factor Receptor ◽  
In Silico Analysis ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Alternative Protein ◽  
Cancer Tissues

Background: Breast cancer affects over 2 million women yearly. Its early detection allows for successful treatment, which motivates to research factors that enable an accurate diagnosis. miR-125a is one of them, correlating with different types of cancer. For example, the miR-125a level decreases in breast cancer tissues; polymorphisms in the miR-125a encoding gene are related to prostate cancer and the risk of radiotherapy-induced pneumonitis. Methods: In this work, we investigated two variants of rs12976445 polymorphism in the context of breast cancer. We analyzed the data of 175 blood samples from breast cancer patients and compared them with the control data from 129 control samples. Results: We observed the tendency that in breast cancer cases TT genotype appeared slightly more frequent over CC and CT genotypes (statistically nonsignificant). The TT genotype appeared also to be more frequent among human epidermal growth factor receptor 2 (HER2) positive patients, compared to HER2 negative. In silico modelling showed that the presence of uridine (U) diminished the probability of pri-miR-125a binding to NOVA1 and HNRNPK proteins. We demonstrated that U and C -variants could promote different RNA folding patterns and provoke alternative protein binding. Conclusions: U-variant may imply a lower miR-125a expression in breast cancer.

Increased NID1 Expression among Breast Cancer Lung Metastatic Women; A Comparative Analysis between Naive and Treated Cases

2020 ◽  
Vol 15 (1) ◽  
pp. 59-69
Author(s):  
Tabinda Urooj ◽  
Bushra Wasim ◽  
Shamim Mushtaq ◽  
Ghulam Haider ◽  
Syed N.N. Shah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Metastasis ◽  
Cancer Progression ◽  
In Silico ◽  
In Silico Analysis ◽  
Treated Group ◽  
Functional Association ◽  
Real Time Quantitative Pcr ◽  
Protein Expressions ◽  
Silico Analysis

Background: Lungs are the second most common reported site of distant metastasis in Breast cancer after bone. Mostly the studies were conducted in cell lines and animal model. To date, there is no blood biomarker reported that could determine the breast cancer progression in terms of lung metastasis. Objective: The aim of this study is to determine Nidogen-1 (NID1)’s mRNA and protein expressions in non-invasive blood samples of breast cancer, in early (II) and lung metastasis advanced stages (III & IV) of naive and treated groups. To determine the functional association of NID1, we employed an in silico analysis, STRING database version 11. Methods: A total of n = 175 cases of breast cancer were recruited in our study. Real time quantitative PCR and ELISA were performed to analyze the mRNA and protein expressions of NID1 respectively. An in silico method is also used to assess NID1’s interactome. Some significant patents related to this topic were also studied and discussed in this research paper. Results: The results show high levels of NID1’s mRNA in the naive group (Group A) as compared to treated group (Group B). Similar trend of increased NID1’s protein expressions was also observed among naive and treated groups, respectively. Our results also show the significant impact of treatment on NID1’s gene and protein expressions. In silico analysis has revealed the functional association of NID1 with its different interactome protein partners. Conclusions: The increased expression of NID1 in early to advanced naive as compared to the treated groups with lung metastasis makes it a promising marker which has pro-metastatic role in breast cancer.

Increased YAP1 expression is significantly associated with breast cancer progression, metastasis and poor survival

2021 ◽  
Author(s):  
Javeria Qadir ◽  
Syeda Kiran Riaz ◽  
Kiran Taj ◽  
Natasha Sattar ◽  
Namood-e Sahar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Hippo Pathway ◽  
Transcriptional Coactivator ◽  
Breast Cancer Patients ◽  
Poor Survival ◽  
Protein Levels ◽  
The Hippo Pathway

YAP1 plays a key role as a transcriptional coactivator in the Hippo pathway. Based on conflicting reports regarding YAP1 function in cancer, this study discerned its role in breast carcinogenesis. First, a systematic review of salient breast cancer studies targeting YAP1 dysregulation was performed. Additionally, freshly excised tumor specimens of approximately 200 breast cancer patients were processed for quantification of YAP1 expression at mRNA and protein levels using quantitative PCR and immunohistochemistry, respectively. YAP1 expression was nine folds higher in tumors versus controls and significantly associated with metastasis (p < 0.05) and poor survival in Pakistani breast cancer patients. These findings establish the role of YAP1 overexpression in tumorigenesis and metastasis. Hence, YAP1 inhibition may be considered a possible therapeutic strategy.

scholarly journals Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway

2020 ◽  
Vol 21 (23) ◽  
pp. 9227
Author(s):  
Nam Ji Sung ◽  
Na Hui Kim ◽  
Young-Joon Surh ◽  
Sin-Aye Park
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Lung Metastasis ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Gremlin 1

Gremlin-1 (GREM1), one of the bone morphogenetic protein (BMP) antagonists, can directly bind to BMPs. GREM1 is involved in organogenesis, tissue differentiation, and organ fibrosis. Recently, numerous studies have reported the oncogenic role of GREM1 in cancer. However, the role of GREM1 in metastasis of breast cancer cells and its underlying mechanisms remain poorly understood. The role of GREM1 in breast cancer progression was assessed by measuring growth, migration, and invasion of breast cancer cells. An orthotopic breast cancer mouse model was used to investigate the role of GREM1 in lung metastasis of breast cancer cells. GREM1 knockdown suppressed the proliferation of breast cancer cells, while its overexpression increased their growth, migration, and invasion. Cells with Grem1-knockdown showed much lower tumor growth rates and lung metastasis than control cells. GREM1 enhanced the expression of matrix metalloproteinase 13 (MMP13). A positive correlation between GREM1 and MMP13 expression was observed in breast cancer patients. GREM1 activated signal transducer and activator of transcription 3 (STAT3) transcription factor involved in the expression of MMP13. Our study suggests that GREM1 can promote lung metastasis of breast cancer cells through the STAT3-MMP13 pathway. In addition, GREM1 might be a promising therapeutic target for breast cancer metastasis.

Sign in / Sign up

Export Citation Format

Share Document