scholarly journals High methionyl–tRNA synthetase expression predicts poor prognosis in patients with breast cancer

2020 ◽  
Vol 73 (12) ◽  
pp. 803-812
Author(s):  
Qin Jin ◽  
Gang Liu ◽  
Biao Wang ◽  
Shubin Li ◽  
Kan Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Poor Prognosis ◽  
Trna Synthetase ◽  
Tnm Stage ◽  
Expression Level ◽  
Mesenchymal Transition ◽  
Methionyl Trna Synthetase ◽  
Mcf 7

AimsMethionyl–tRNA synthetase (MARS) is known to play a critical role in initiating translation and protection against cellular damages in vivo. The aim of this study was to clarify the role of MARS in breast cancer (BC) progression.MethodsThe expressions of MARS messenger RNA (mRNA) and protein in human BC tissues and adjacent non-cancerous tissues were detected by quantitative real-time PCR, western blot and immunohistochemistry. The prognostic potential of MARS in patients with BC was assessed by univariate and multivariate survival analyses. The association between the MARS expression and BC progression was further evaluated by the bioinformatics database of UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Database of Normal and Tumor Tissues (GENT). The role of MARS in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of human breast cancer cell line (MCF-7 cells) was investigated after siRNA transfection.ResultsThe expression level of MARS mRNA in the fresh BC tissues was significantly higher than that in the adjacent tissues. Immunohistochemistry showed that the expression level of MARS was closely associated with the clinicopathologial parameters of patients with BC, including the HER-2 status, Ki-67 status, molecular classification, tumour grade, N stage and tumour, node, metastasis (TNM) stage, and this finding was further confirmed by UALCAN database. The Kaplan-Meier analysis showed that high MARS expression and TNM stage were predictors of poor prognosis of patients with BC. The proliferation, migration and EMT capabilities of MCF-7 cells were significantly suppressed after MARS knockdown. An overview of UALCAN, GEPIA and GENT results suggested that MARS may be an oncogene of BC, as well as a potential therapeutic target of this malignant tumour.ConclusionsHigh expression level of MARS in the human BC tissues was significantly associated with the unfavourable prognosis of patients with BC, suggesting that MARS may serve as a potential prognostic marker for the clinical diagnosis and prognostic prediction of BC.

scholarly journals Mummy Induces Apoptosis Through Inhibiting of Epithelial-Mesenchymal Transition (EMT) in Human Breast Cancer Cells

2020 ◽  
Vol 9 ◽  
pp. 1812
Author(s):  
Solmaz Rahmani Barouji ◽  
Arman Shahabi ◽  
Mohammadali Torbati ◽  
Seyyed Mohammad Bagher Fazljou ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Mcf 7

Background: Mummy (Iranian pure shilajit) is a remedy with possessing anti-inflammatory, antioxidant and anticancer activities. This study aimed to examine mummy effects on epithelial-mesenchymal transition (EMT) and invasiveness of MCF-7 and MDA-MB-231 breast cancer (BC) cell lines with underlying its mechanism. Materials and Methods: The dose-dependent inhibitory effect of the mummy on cell proliferation in vitro was determined using the MTT assay.  Flow cytometry and 4’,6-diamidino-2-phenylindole dihydrochloride staining were respectively used for quantitative and qualitative analysis of cellular apoptosis, and gene expression analysis was conducted using real-time PCR. Results: MDA-MB-231 showed more sensitivity than the MCF-7 cell line to the anticancer activity of mummy, while mummy did not exhibit significant cell cytotoxicity against human normal cells (MCF-10A). The gene expression profile demonstrated a significant decrease in TGF-β1, TGF-βR1, TWIST1, NOTCH1, CTNNB1, SRC along with an increase in E-cadherin mRNA levels in mummy treated cells compared to the untreated control group (P≤0.05). Conclusion: Mummy triggers inhibition of EMT and metastasis in breast cancer cells mainly through the downregulation of TGFβ1 activity, and more studies required to find its specific anticancer activity with details. [GMJ.2020;9:e1812]

scholarly journals MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1557
Author(s):  
Elif Damla Arisan ◽  
Ozge Rencuzogullari ◽  
Clara Cieza-Borrella ◽  
Francesc Miralles Arenas ◽  
Miriam Dwek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Therapeutic Success ◽  
Mesenchymal Transition ◽  
Signaling Axis ◽  
Mcf 7

Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.

scholarly journals Decreased HECTD1 mRNA expression is associated with poor prognosis and enhanced mitochondrial cellular respiratory function in breast cancer

2021 ◽  
Author(s):  
Yasuaki Uemoto ◽  
Eriko Katsuta ◽  
Naoto Kondo ◽  
Yumi Wanifuchi-Endo ◽  
Takashi Fujita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Protein Expression ◽  
Mrna Expression ◽  
Respiratory Function ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Negative Regulator ◽  
Mesenchymal Transition

Abstract HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts using mRNA and protein expression, and bioinformatics. We examined the prognostic significance of HECTD1 by multivariate analysis. HECTD1 mRNA expression (HECTD1 expression) was lower in breast cancer compared with adjacent normal tissues. HECTD1 expression levels also differed among breast cancer subtypes. Decreased HECTD1 expression was significantly associated with aggressive tumour characteristics, including large tumour size and high histological grade. HECTD1 expression was inversely associated with mitochondrial cellular respiratory function and reactive oxygen species in breast cancer tissues. Multivariate analysis identified low HECTD1 mRNA expression level as an independent risk factor for disease-free (P = 0.009) and overall (P = 0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with mRNA expression and prognosis. HECTD1 mRNA expression is a candidate prognostic biomarker in breast cancer. The poor prognosis of patients with low HECTD1 mRNA expression may be associated with increased mitochondrial respiratory function.

scholarly journals Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells

2007 ◽  
Vol 39 (4) ◽  
pp. 289-304 ◽  
Author(s):  
Shaheen Khan ◽  
Fei Wu ◽  
Shengxi Liu ◽  
Qian Wu ◽  
Stephen Safe
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Retinoic Acid Receptor ◽  
Estrogen Receptor Α ◽  
Mrna Levels ◽  
Aspartate Transcarbamylase ◽  
Mcf 7

AbstractDeletion analysis of several 17β-estradiol (E2)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E2-responsive GC-rich promoters from the E2F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor α (RARα) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E2-induced transactivation. The contributions of individual Sp proteins to basal and E2-induced activity were promoter dependent. iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E2F1, CAD, and RARα mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor α/Sp-mediated gene expression in MCF-7 cells.

scholarly journals Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: Role of the proximal promoter GC-rich region

2012 ◽  
Vol 84 (5) ◽  
pp. 722-735 ◽  
Author(s):  
Neal A. Englert ◽  
Robert J. Turesky ◽  
Weiguo Han ◽  
Erin E. Bessette ◽  
Simon D. Spivack ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Epigenetic Regulation ◽  
Breast Cancer Cells ◽  
Proximal Promoter ◽  
Rich Region ◽  
Ahr Gene ◽  
Mcf 7

scholarly journals The role of miRNA in regulation of AXL, DAPK1, NFIB gene expression in breast cancer

2018 ◽  
pp. 130-133
Author(s):  
И.В. Пронина ◽  
Е.А. Филиппова ◽  
С.С. Лукина ◽  
А.М. Бурденный ◽  
Т.П. Казубская ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Epithelial Mesenchymal Transition ◽  
Negative Regulator ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Protein Encoding ◽  
Apoptotic Pathways ◽  
Encoding Genes

Рак молочной железы (РМЖ) характеризуется эпигенетическими нарушениями, которые приводят к нарушению регуляции экспрессии опухоль ассоциированных белок-кодирующих генов, что влияет на развитие опухоли. Цель исследования - поиск новых микроРНК, потенциально вовлеченных в регуляцию экспрессии 3 белок-кодирующих генов (AXL, DAPK1, NFIB), связанных с регуляцией апоптоза и эпителиально-мезенхимального перехода при РМЖ. Методом количественной ПЦР определены изменения экспрессии 3 белок-кодирующих генов (AXL, DAPK1, NFIB) и 3 микроРНК (miR-127-5p, -132-3р, -9-5p), предсказанных с помощью алгоритмов miRWalk 2.0 как регуляторные. Определены статистически значимые отрицательные корреляции между изменениями уровней экспрессии микроРНК и мРНК для следующих пар: miR-127-5p - DAPK1 (Rs = -0,503, p = 0,001) и miR-9-5p - DAPK1 (Rs = -0,335, p = 0,040). Таким образом, установлена потенциальная роль двух микроРНК в регуляции экспрессии гена DAPK1, активатора различных путей апоптоза и негативного регулятора ЭМП, что имеет фундаментальное значение и может найти применение для разработки таргетной терапии РМЖ. Breast cancer (BC) is characterized by epigenetic disorders, which lead to dysregulation of protein-coding gene expression; together these result in development of a tumor. The goal of the study was to search for new miRNAs that are potentially involved in regulation of the expression of three protein-encoding genes (AXL, DAPK1, NFIB) associated with regulation of apoptosis and the epithelial-mesenchymal transition in breast cancer. Quantitative PCR was used to determine changes in the expression of three protein-coding genes (AXL, DAPK1, NFIB) and three miRNAs (miR-127-5p, -132-3p, -9-5p) that had been predicted to be regulators by miRWalk 2.0 algorithms. Statistically significant negative correlations between changes in miRNA and mRNA expression were determined for the following pairs: miR-127-5p - DAPK1 (Rs = -0.503, p = 0.001) and miR-9-5p - DAPK1 (Rs = -0.335, p = 0.040). Therefore, the study showed a potential role of two miRNAs in regulation of the DAPK1 gene expression, an activator of various apoptotic pathways and a negative regulator of EMT. This result is fundamentally important and can be used to develop targeted therapies for breast cancer.

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

2019 ◽  
Vol 16 (2) ◽  
pp. 184-197 ◽  
Author(s):  
Hossein Bakhtou ◽  
Asiie Olfatbakhsh ◽  
Abdolkhaegh Deezagi ◽  
Ghasem Ahangari
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Dopamine Receptors ◽  
Breast Cancer Cells ◽  
D2 Receptors ◽  
Healthy Individuals ◽  
Agonist And Antagonist ◽  
The Mean ◽  
Mcf 7

Background:Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3.Methods:The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells.Results:Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations.Conclusion:This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.

scholarly journals The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Data ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lymphatic Vessels ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cancer Tissue ◽  
Expression Levels

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

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