scholarly journals Regulation of Breast Cancer and Bone Metastasis by MicroRNAs

2013 ◽  
Vol 35 ◽  
pp. 369-387 ◽  
Author(s):  
S. Vimalraj ◽  
P. J. Miranda ◽  
B. Ramyakrishna ◽  
N. Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Metastasis ◽  
Cancer Progression ◽  
Human Breast ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Complex Process ◽  
And Function

Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

scholarly journals Oestrogen receptors and antioestrogen treatment of hormone-dependent tumours

2018 ◽  
Vol 49 (2) ◽  
pp. 91
Author(s):  
N. G. KOSTOMITSOPOULOS (Ν.Γ. ΚΩΣΤΟΜΗΤΣΟΠΟΥΛΟΣ)
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Sequences ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Specific Gene ◽  
Oestrogen Receptors ◽  
Human Breast ◽  
Potential Use

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

scholarly journals The emerging role of circular RNAs in breast cancer

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Si-ying Zhou ◽  
Wei Chen ◽  
Su-jin Yang ◽  
Zi-han Xu ◽  
Jia-hua Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Invasion ◽  
Clinical Characteristics ◽  
Circular Rnas ◽  
Rnase R ◽  
New Class ◽  
Regulatory Rnas ◽  
And Function

AbstractBreast cancer (BCa) is one of the most frequently diagnosed cancers and leading cause of cancer deaths among females worldwide. Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by circular shape resulting from covalently closed continuous loops that are capable of regulating gene expression at transcription or post-transcription levels. With the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Recently, an increasing number of circRNAs are discovered and reported to show different expression in BCa and these dysregulated circRNAs were correlated with patients’ clinical characteristics and grade in the progression of BCa. CircRNAs participate in the bioprocesses of carcinogenesis of BCa, including cell proliferation, apoptosis, cell cycle, tumorigenesis, vascularization, cell invasion, migration as well as metastasis. Here we concentrated on biogenesis and function of circRNAs, summarized their implications in BCa and discussed their potential as diagnostic and therapeutic targets for BCa.

scholarly journals Bromodomain-Containing Protein 4: A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Jude Alsarraj ◽  
Kent W. Hunter
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Susceptibility Gene ◽  
Breast Cancer Metastasis ◽  
Primary Tumors ◽  
Inherited Susceptibility ◽  
Complex Process ◽  
Host Genetic

Metastasis is an extremely complex process that accounts for most cancer-related deaths. Malignant primary tumors can be removed surgically, but the cells that migrate, invade, and proliferate at distant organs are often the cells that prove most difficult to target therapeutically. There is growing evidence that host factors outside of the primary tumors are of major importance in the development of metastasis. Recently, we have shown that the bromodomain-containing protein 4 or bromodomain 4 (Brd4) functions as an inherited susceptibility gene for breast cancer progression and metastasis. In this paper, we will discuss that host genetic background on which a tumor arises can significantly alter the biology of the subsequent metastatic disease, and we will focus on the role ofBrd4in regulating metastasis susceptibility.

scholarly journals Low E2F2 activity is associated with high genomic instability and PARPi resistance

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jonathan P. Rennhack ◽  
Eran R. Andrechek
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Dna Repair ◽  
Human Breast Cancer ◽  
Metabolic Reprogramming ◽  
Patient Treatment ◽  
Expression Data ◽  
Human Breast

Abstract The E2F family, classically known for a central role in cell cycle, has a number of emerging roles in cancer including angiogenesis, metabolic reprogramming, metastasis and DNA repair. E2F1 specifically has been shown to be a critical mediator of DNA repair; however, little is known about DNA repair and other E2F family members. Here we present an integrative bioinformatic and high throughput drug screening study to define the role of E2F2 in maintaining genomic integrity in breast cancer. We utilized in vitro E2F2 ChIP-chip and over expression data to identify transcriptional targets of E2F2. This data was integrated with gene expression from E2F2 knockout tumors in an MMTV-Neu background. Finally, this data was compared to human datasets to identify conserved roles of E2F2 in human breast cancer through the TCGA breast cancer, Cancer Cell Line Encyclopedia, and CancerRx datasets. Through these methods we predict that E2F2 transcriptionally regulates mediators of DNA repair. Our gene expression data supports this hypothesis and low E2F2 activity is associated with a highly unstable tumor. In human breast cancer E2F2, status was also correlated with a patient’s response to PARP inhibition therapy. Taken together this manuscript defines a novel role of E2F2 in cancer progression beyond cell cycle and could impact patient treatment.

The role of microRNAs in human breast cancer progression

Tumor Biology ◽  
2014 ◽  
Vol 35 (7) ◽  
pp. 6235-6244 ◽  
Author(s):  
WenCheng Zhang ◽  
Jinbo Liu ◽  
Guangshun Wang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Human Breast Cancer ◽  
Breast Cancer Progression ◽  
Human Breast

Long non-coding RNA PVT1 regulates the proliferation and metastasis of human breast cancer via the Wnt/b-catenin signalling pathway

2021 ◽  
Author(s):  
Nianqu Zhang ◽  
Qing Li ◽  
Shanmei Sun
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Apoptotic Cell ◽  
Migration And Invasion ◽  
Human Breast ◽  
Gene Expression Levels

IntroductionThe development of many human diseases has been implicated to be coupled by the dysregulation of long non-coding RNAs (lncRNAs). Considering this, the current study was aimed at identifying and then investigating the molecular role of a specific lncRNA from a set of such genetic elements in regulating the developmental aspects of human breast cancer.Material and methodsThe quantitative real-time polymerase chain reaction (qRT-PCR) method was used to deduce the gene expression levels. Proliferation of cancer cells was determined by the cell counting kit 8 (CCK8). The evaluation of apoptotic cell death in breast cancer cells was made through the acridine orange/ethidium bromide (AO/EB) and annexin V-FITC staining protocols. Transwell assays were used to monitor cell migration and invasion.ResultsEstimation of gene expression levels of a set of lncRNAs showed that lncRNA PVT1 is specifically overexpressed in the breast cancer tissues and cell lines. The downregulation of PVT1 in cancer cells negatively affected their proliferation rates, and cancer cells exhibited significantly lower viabilities due to induction of Bax/Bcl-2 signal arbitrated apoptotic cell death in the cancer cells. Moreover, the cancer cells showed significantly lower rates of migration and invasion when lncRNA PVT1 was repressed. The PVT1 repression-driven anti-cancer effects against the cancer cells were seen to be modulated through the Wnt/β-catenin signalling pathway.ConclusionsThe results of this work are indicative of the prognostic role of lncRNA PVT1 in breast cancer. Also, the molecular targeting of PVT1 might prove to be a vital step against the progression of human breast cancer.

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