scholarly journals miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1790 ◽  
Author(s):  
Marta Sereno ◽  
Mafalda Videira ◽  
Imola Wilhelm ◽  
István A. Krizbai ◽  
Maria Alexandra Brito
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Metastatic Cascade ◽  
Physiological Processes ◽  
Breast Cancer Brain Metastasis ◽  
Health And Disease

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Prasuja Rokkam ◽  
Shailender Gugalavath ◽  
Deepak Kakara Gift Kumar ◽  
Rahul Kumar Vempati ◽  
Rama Rao Malla
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Neural Development ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Basic Function ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

scholarly journals Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

2021 ◽  
Author(s):  
Chun Yang ◽  
Stéphane Croteau ◽  
Pierre Hardy
Keyword(s):  
Histone Deacetylase ◽  
Posttranslational Modifications ◽  
Histone Deacetylases ◽  
Muscle Development ◽  
Target Genes ◽  
Human Cancer ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

scholarly journals Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Expression Patterns ◽  
Survival Rates ◽  
In Silico Analysis ◽  
Cancer Prognosis ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Non Coding Rnas

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

scholarly journals Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman
Keyword(s):  
Animal Studies ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Evolutionary Developmental Biology ◽  
Noncommunicable Disease ◽  
Normal Range ◽  
Physiological Processes ◽  
New Concepts ◽  
Health And Disease ◽  
Underlying Mechanisms

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

scholarly journals Dysregulation of miR-638 in Breast Cancer Patients and Bioinformatics Investigation of Its Target Genes in Apoptosis, Angiogenesis and Autophagy Pathways

2019 ◽  
Vol 12 (11) ◽  
Author(s):  
Samaneh Ahmadi ◽  
Mojtaba Saffari ◽  
Mohammad Hossein Modarressi ◽  
Reza Shirkoohi ◽  
Marjan Jamalian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Target Genes ◽  
Breast Cancer Patients

scholarly journals CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

2020 ◽  
Author(s):  
Bo Fu ◽  
Wei Liu ◽  
Peng Li ◽  
Li Pan ◽  
Ke Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Tumorigenesis And Progression ◽  
And Migration

Abstract Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

scholarly journals Pathways to Breast Cancer Recurrence

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Aamir Ahmad
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Recurrent Disease ◽  
Current Knowledge ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Number Of Factors ◽  
Prevention Of Breast Cancer

Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence.

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.

Young Age is not an Ominous Prognostic Factor in Breast Cancer Patients

1987 ◽  
Vol 73 (3) ◽  
pp. 233-235 ◽  
Author(s):  
Giuseppe Muscolino ◽  
Corrado Villani ◽  
Amedeo Vittorio Bedini ◽  
Alberto Luini ◽  
Bruno Salvadori
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Young Women ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Young Age ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

Analysis of a series of 137 women 20–30 years of age, operated for breast carcinoma, excluding patients pregnant, lactating or with inflammatory cancer, showed that disease-free survival rates were similar and not lower than those reported for a large series of 716 breast cancer patients of all ages, treated and followed at the same Institute. Ten-year disease-free survival rates for the two series of 137 young women and 716 patients of all ages were 43.7% and 47.1% respectively. Even when considering the subgroups of patients with and without nodal axillary involvement, the corresponding figures for the two series considered were 72.6% vs. 72.1% (N−) and 25.1% vs. 24.5% (N+). It can be concluded that young age cannot be considered as an unfavorable prognostic factor.

Different Targeting Strategies for Treating Breast Cancer Bone Metastases

2018 ◽  
Vol 24 (28) ◽  
pp. 3320-3331 ◽  
Author(s):  
Iram Irshad ◽  
Pegah Varamini
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Bone Metastasis ◽  
Treatment Options ◽  
Tumor Burden ◽  
Breast Cancer Patients ◽  
Physiological Processes ◽  
Metastatic Cells ◽  
Skeletal Complications

Background: Breast cancer is the most frequently diagnosed malignancy in women worldwide. Breast cancer tends to metastasize to bone. Around 70% of the breast cancer patients eventually develop bone metastasis. After the bone invasion, metastatic cells disrupt the balance between osteoblastic and osteoclastic activities, leading to skeletal complications, characterized by pain and pathological fractures and hence worsening the patient's quality of life. Once tumor invades the bone, it is hard to treat it with, the so-far available treatments options (e.g. bisphosphonates and denosumab). Bone metastasis should be essentially controlled, in cancer treatment and there is a strong need to explore new, more efficient therapeutic targets. This review discusses the bone physiological processes and the recent advances in exploring different pathways involved in bone metastasis. Furthermore, some novel treatment options, which are under preclinical and clinical investigations, are highlighted. Conclusion: A deeper understanding of these metastatic pathways can provide oncology researchers with novel avenues for treating bone metastasis, one of the main challenges to cure breast cancer. The restoration of healthy bone environment will not only improve the patient's quality of life but also reduces the tumor burden.

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