scholarly journals Contribution of miRNAs in the Pathogenesis of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Ali Khanbabapour Sasi ◽  
Atefe Abak ◽  
Hamed Shoorei ◽  
Ali Khoshkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiling ◽  
Epithelial Mesenchymal Transition ◽  
Breast Carcinogenesis ◽  
Mesenchymal Transition ◽  
Non Invasive ◽  
Heterogeneous Nature ◽  
Almost All ◽  
Resistance To Chemotherapy

Breast cancer is the most frequently diagnosed cancer among females. Gene expression profiling methods have shown the deregulation of several genes in breast cancer samples and have confirmed the heterogeneous nature of breast cancer at the genomic level. microRNAs (miRNAs) are among the recently appreciated contributors in breast carcinogenic processes. These small-sized transcripts have been shown to partake in breast carcinogenesis through modulation of apoptosis, autophagy, and epithelial–mesenchymal transition. Moreover, they can confer resistance to chemotherapy. Based on the contribution of miRNAs in almost all fundamental aspects of breast carcinogenesis, therapeutic intervention with their expression might affect the course of this disorder. Moreover, the presence of miRNAs in the peripheral blood of patients potentiates these transcripts as tools for non-invasive diagnosis of breast cancer.

scholarly journals NRF1-Mediated Oncogenic Reprogramming Drives Estrogen-Induced Breast Carcinogenesis

2018 ◽  
Author(s):  
Jayanta Kumar Das ◽  
Quentin Felty ◽  
Robert Poppiti ◽  
Robert M. Jackson ◽  
Deodutta Roy
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Epithelial Mesenchymal Transition ◽  
Confocal Imaging ◽  
Cancer Tissue ◽  
Causative Role ◽  
Dependent Manner ◽  
Breast Carcinogenesis ◽  
Human Breast Cancer Tissue ◽  
Mesenchymal Transition

Transcription factor activity of the nuclear respiratory factor 1 protein (NRF1) is increased in breast cancer. Whether this gain of NRF1 activity is directly involved in breast cancer remains unknown. Herein, we report a novel oncogenic function of NRF1 supporting its causative role in breast cancer development and progression. The gain of NRF1 and/or treatment with 17β-estradiol (E2) produced heterogeneous breast cancer stem cells (BCSCs) composed of more than ten distinct cell sub-populations. Flow sorting combined with confocal imaging of markers for pluripotency, epithelial mesenchymal transition (EMT), and BCSCs phenotypically confirmed that the sub-populations of BCSCs arise from cell re-programming. Thus, we determined the molecular actions of NRF1 on its target gene CXCR4 because of its known role in the acquisition of BCSCs through EMT. CXCR4 was activated by NRF1 in a redox dependent manner during malignant transformation. NRF1-induced BCSCs were able to form xenograft tumors in vivo, while inhibiting transcription of CXCR4 prevented xenograft tumor growth. Consistent with our observation of NRF1 driven breast tumorigenesis in the experimental model, higher levels of NRF1 protein expression were also found in human breast cancer tissue specimens. This highly novel role of NRF1 in the stochastic acquisition of BCSCs and their progression to a malignant phenotype may open an entirely new research direction targeting NRF1 signaling in invasive breast cancer. Additionally, the discovery of targeting transcriptional activation of CXCR4 to inhibit NRF1-induced oncogenic transformation provides a mechanistic explanation for estrogen-dependent breast carcinogenesis and opens the new avenues for mechanistic therapeutic strategy against breast cancer.

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 An unsupervised feature extraction and selection strategy for identifying epithelial-mesenchymal transition state metrics in breast cancer and melanoma

2019 ◽  
Author(s):  
David J. Klinke ◽  
Arezo Torang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Cell Phenotype ◽  
Holistic View ◽  
Mesenchymal Transition ◽  
Feature Extraction And Selection ◽  
Cellular Context ◽  
Immune Contexture

Digital cytometry is opening up new avenues to better understand the heterogeneous cell types present within the tumor microenvironment. While the focus is towards elucidating immune and stromal cells as clinical correlates, there is still a need to better understand how a change in tumor cell phenotype, such as the epithelial-mesenchymal transition, influences the immune contexture. To complement existing digital cytometry methods, our objective was to develop an unsupervised gene signature capturing a change in differentiation state that is tailored to the specific cellular context of breast cancer and melanoma, as a illustrative example. Towards this aim, we used principal component analysis coupled with resampling to develop unsupervised gene expression-based state metrics specific for the cellular context that characterize the state of cellular differentiation within an epithelial to mesenchymal-like state space and independently correlate with metastatic potential. First developed using cell line data, the orthogonal state metrics were refined to exclude the contributions of normal fibroblasts and to provide tissue-level state estimates based on bulk tissue RNA-seq measures. The resulting gene expression-based metrics for differentiation state aim to inform a more holistic view of how the malignant cell phenotype influences the immune contexture within the tumor microenvironment.

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