Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals The Role of lncRNA in the Development of Tumors, Including Breast Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8427
Author(s):  
Beata Smolarz ◽  
Anna Zadrożna-Nowak ◽  
Hanna Romanowicz
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Present Article ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulation Of Transcription ◽  
Ribonucleic Acids ◽  
Detailed Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) are the largest groups of ribonucleic acids, but, despite the increasing amount of literature data, the least understood. Given the involvement of lncRNA in basic cellular processes, especially in the regulation of transcription, the role of these noncoding molecules seems to be of great importance for the proper functioning of the organism. Studies have shown a relationship between disturbed lncRNA expression and the pathogenesis of many diseases, including cancer. The present article presents a detailed review of the latest reports and data regarding the importance of lncRNA in the development of cancers, including breast carcinoma.

Abstract P141: GYY4137, a H 2 S Donor, Normalizes miR-132 Targeted Sirt1 and Ace2 Expression to Improve Kidney Function in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Gregory Weber ◽  
Sathnur Pushpakumar ◽  
Utpal Sen
Keyword(s):  
Blood Flow ◽  
Kidney Function ◽  
Expression Patterns ◽  
Sirtuin 1 ◽  
Ang Ii ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Epigenetic Gene Silencing ◽  
Increased Blood Flow

MicroRNAs regulate several physiological processes and are implicated in various pathologies, including hypertension. Previous work indicates miR-132 targets Sirtuin 1 (Sirt1), a histone deacetylase and regulator of epigenetic gene silencing in various cellular processes. Sirt1 is expressed in the kidney; however, its role in hypertensive kidney and whether it is regulated by physiological gaseous molecules, such as hydrogen sulfide (H 2 S), is not known. In this study, we sought to determine the role of miR-132 in regulating Sirt1, Ace2 and At1 in hypertensive kidney and whether H 2 S donor, GYY4137 (GYY), could reverse these effects and mitigates renal dysfunction. Wild-type mice were treated without or with Ang-II (1000 ng/Kg/Min) and GYY (133 μM) for 4 weeks. Quantitative PCR, Western blot, and immunofluorescence assays were performed. Increased expression levels of miR-132 in hypertensive mice (3.79 fold vs control) were reduced in mice receiving GYY treatment (2.43 fold vs control). Sirt1 expression was reduced (-1.15 fold) in Ang-II mice but was upregulated in GYY (1.25 fold) and Ang-II+GYY (1.9 fold) groups. A similar effect was seen with Sirt1 protein where the expression was increased in animals treated with GYY and Ang-II+GYY (1.16, 1.03 respectively) compared to Ang-II (0.47). Ace2 in Ang-II+GYY (0.45) was increased compared to Ang-II (0.17), while At1 was reduced (0.46) compared to Ang-II (0.86). Immunofluorescence showed decreased signal of Sirt1 in the glomerulus in Ang-II mice and increased At1 in the blood vessels surrounding the glomerulus, leading to constriction of renal artery, decreased blood flow, and kidney dysfunction. These effects were alleviated in mice treated with GYY. Our data suggests that upregulation of miR-132 in hypertensive kidney decreases Sirt1 and Ace2 expression, leading to increased Ang-II signaling through the At1 receptor and GYY supplementation reverses these expression patterns, leading to increased blood flow and kidney function.

Mice homozygous for a targeted disruption of Hoxd-3 (Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 579-595 ◽  
Author(s):  
B.G. Condie ◽  
M.R. Capecchi
Keyword(s):  
Hox Genes ◽  
Es Cells ◽  
Cervical Vertebrae ◽  
Expression Patterns ◽  
Cervical Vertebra ◽  
Targeted Disruption ◽  
Paralogous Genes ◽  
Variable Extent ◽  
Basioccipital Bone

Gene targeting in embryo-derived stem (ES) cells was used to generate mice with a disruption in the homeobox-containing gene Hoxd-3 (Hox-4.1). Mice homozygous for this mutation show a radically remodeled craniocervical joint. The anterior arch of the atlas is transformed to an extension of the basioccipital bone of the skull. The lateral masses of the atlas also assume a morphology more closely resembling the exoccipitals and, to a variable extent, fuse with the exoccipitals. Formation of the second cervical vertebra, the axis, is also affected. The dens and the superior facets are deleted, and the axis shows ‘atlas-like’ characteristics. An unexpected observation is that different parts of the same vertebra are differentially affected by the loss of Hoxd-3 function. Some parts are deleted, others are homeotically transformed to more anterior structures. These observations suggest that one role of Hox genes may be to differentially control the proliferation rates of the mesenchymal condensations that give rise to the vertebral cartilages. Within the mouse Hox complex, paralogous genes not only encode very similar proteins but also often exhibit very similar expression patterns. Therefore, it has been postulated that paralogous Hox genes would perform similar roles. Surprisingly, however, no tissues or structures are affected in common by mutations in the two paralogous genes, Hoxa-3 and Hoxd-3.

The Role of Early Growth Response 1 in the Prognostic Value and Cell Migration of Breast Cancer

2021 ◽  
Author(s):  
Leiyu Hao ◽  
Fengru Huang ◽  
Xinqian Yu ◽  
Bujie Xu ◽  
Yan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Protein Expression ◽  
Prognostic Value ◽  
Growth Response ◽  
Expression Patterns ◽  
Early Growth ◽  
The Cancer Genome Atlas ◽  
Early Growth Response

Abstract Background: Early growth response family members (EGRs), EGR1-4, have increasingly attracted attention in multiple cancers. However, the exact expression patterns and prognostic values of EGRs in the progress of breast cancer (BRCA) remain largely unknown. Methods: The mRNA expression and prognostic characteristics of EGRs were examined by the Cancer Genome Atlas (TCGA), Oncomine and Kaplan-Meier plotter. Enrichment analyses were conducted based on protein-protein interaction (PPI) network. The Tumor Immune Estimation Resource (TIMER) database and MethSurv were further explored. The protein expression level of EGR1 and cell migration were measured by Western blotting, immunohistochemistry, wound-healing assay and Boyden chamber assay in BRCA. Results: The transcriptional levels of EGR1/2/3 displayed significantly low expression in BRCA compared to that in normal tissues, while EGR4 was shown adverse expression pattern. Survival analysis revealed up-regulated EGR1-4 were remarkably associated with favorable relapse-free survival (RFS). A close correlation with specific tumor-infiltrating immune cells (TIICs) and several CpG sites of EGRs were exhibited. Immunohistochemistry assays showed that the protein expression of EGR1 was remarkably downregulated in BRCA compared to that in paracancerous tissues. Cell migration of MCF10A cells was increased after the silence of EGR1 by siRNA transfection.Conclusions: This study provides a novel insight to the role of EGR1 in the prognostic value and cell migration of BRCA.

The role of three‐dimensional printing in the surgical management of breast cancer

2019 ◽  
Vol 120 (6) ◽  
pp. 897-902 ◽  
Author(s):  
Lumarie Santiago ◽  
Beatriz E. Adrada ◽  
Abigail S. Caudle ◽  
Mark W. Clemens ◽  
Dalliah M. Black ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Surgical Management ◽  
Three Dimensional ◽  
Three Dimensional Printing ◽  
Dimensional Printing

scholarly journals Overview of RNA G-quadruplex structures

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Magdalena Małgowska
Keyword(s):  
Three Dimensional ◽  
Telomere Maintenance ◽  
Structural Studies ◽  
Biological Functions ◽  
Cellular Processes ◽  
Novel Drugs ◽  
G Quadruplex ◽  
Conformational Diversity

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.

scholarly journals Mending a broken heart: the role of mitophagy in cardioprotection

2015 ◽  
Vol 308 (3) ◽  
pp. H183-H192 ◽  
Author(s):  
Alexandra G. Moyzis ◽  
Junichi Sadoshima ◽  
Åsa B. Gustafsson
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Cellular Processes ◽  
Differentiated Cells ◽  
Calcium Storage ◽  
Response To Stress ◽  
Metabolite Synthesis ◽  
Energy Dependent

The heart is highly energy dependent with most of its energy provided by mitochondrial oxidative phosphorylation. Mitochondria also play a role in many other essential cellular processes including metabolite synthesis and calcium storage. Therefore, maintaining a functional population of mitochondria is critical for cardiac function. Efficient degradation and replacement of dysfunctional mitochondria ensures cell survival, particularly in terminally differentiated cells such as cardiac myocytes. Mitochondria are eliminated via mitochondrial autophagy or mitophagy. In the heart, mitophagy is an essential housekeeping process and required for cardiac homeostasis. Reduced autophagy and accumulation of impaired mitochondria have been linked to progression of heart failure and aging. In this review, we discuss the pathways that regulate mitophagy in cells and highlight the cardioprotective role of mitophagy in response to stress and aging. We also discuss the therapeutic potential of targeting mitophagy and directions for future investigation.

scholarly journals Role of miR-10b-5p in the prognosis of breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Development ◽  
Clinicopathological Parameters ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ppi Networks

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.

scholarly journals DNA sequence encodes the position of DNA supercoils

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sung Hyun Kim ◽  
Mahipal Ganji ◽  
Eugene Kim ◽  
Jaco van der Torre ◽  
Elio Abbondanzieri ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Structural Information ◽  
Three Dimensional ◽  
Decisive Role ◽  
Chromosomal Dna ◽  
Dna Structures ◽  
Cellular Processes ◽  
Specific Sequences ◽  
Good Agreement

The three-dimensional organization of DNA is increasingly understood to play a decisive role in vital cellular processes. Many studies focus on the role of DNA-packaging proteins, crowding, and confinement in arranging chromatin, but structural information might also be directly encoded in bare DNA itself. Here, we visualize plectonemes (extended intertwined DNA structures formed upon supercoiling) on individual DNA molecules. Remarkably, our experiments show that the DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific sequences. We develop a physical model that predicts that sequence-dependent intrinsic curvature is the key determinant of pinning strength and demonstrate this simple model provides very good agreement with the data. Analysis of several prokaryotic genomes indicates that plectonemes localize directly upstream of promoters, which we experimentally confirm for selected promotor sequences. Our findings reveal a hidden code in the genome that helps to spatially organize the chromosomal DNA.

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