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

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.

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

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666200302115438 ◽

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.

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A common transition in multi-drug resistance gene and risk of breast cancer: A genetic association study with an in silico-analysis

Bioscience Biotechnology Research Communications ◽

10.21786/bbrc/9.4/11 ◽

2016 ◽

Vol 9 (4) ◽

pp. 643-652

Author(s):

Davood Kheirkhah ◽

Mohammad Karimian

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Association Study ◽

Resistance Gene ◽

In Silico ◽

Genetic Association Study ◽

In Silico Analysis ◽

Multi Drug Resistance ◽

Common Transition ◽

Silico Analysis

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The Expression of miR-513c and miR-3163 was Downregulated in Tumor Tissues Compared with Margin Tissues of Patients With Breast Cancer

10.21203/rs.3.rs-28926/v1 ◽

2020 ◽

Author(s):

Soheila Delgir ◽

Khandan Ilkhani ◽

Asma Safi ◽

Farhad Seif ◽

Milad Bastami ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

In Silico ◽

In Silico Analysis ◽

Glutamine Metabolism ◽

Expression Level ◽

P Value ◽

Biological Processes ◽

Tumor Tissues ◽

Silico Analysis

Abstract Background Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered a critical nutrition for tumor cell growth and therefore, targeting glutamine metabolism, especially Glutaminase, which catalyzed the conversion of glutamine to glutamate can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with short length and single strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer.Methods Since, in-silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism, the expression level of these two miRNAs was evaluated in eighty BC tissues and margin tissues. The data were analyzed to evaluate the correlation between expression level of these miRNAs and patient’s characteristics such as abortion history, family history, and age. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on its gene targets.Results In-silico studies revealed the top categories of biological processes and pathways that play a critical role in cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (P-value = 0.02062 and fold change= -2.3801) and miR-3163 (P-value = 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup studies did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion.Conclusion Based on our data, miR-513c and miR-3163 may be offered as a potential diagnosis and therapeutic targets for patients with BC.

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