scholarly journals Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas

2021 ◽  
Vol 67 (2) ◽  
pp. 33-43
Author(s):  
Zeeshan Javed ◽  
Khushbukhat Khan ◽  
Qamar Raza ◽  
Haleema Sadia ◽  
Faiez Ahmad Shah ◽  
...  

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

2020 ◽  
Vol 6 (1) ◽  
pp. 18
Author(s):  
Matthias Egger ◽  
Jeffrey D. Jenks ◽  
Martin Hoenigl ◽  
Juergen Prattes

Invasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and improving the diagnostic process are ambitiously searched for. In this context, polymerase chain reaction (PCR) may represent a potential candidate. Its additional value and benefits in diagnosis have been demonstrated and are scientifically established. Nevertheless, standardized and widespread usage is sparse because several factors influence diagnostic quality and need to be considered in order to optimize diagnostic performance and outcome. In the following review, the current role of PCR in the diagnosis of IA is explored, with special focus on the strengths and limitations of PCR in different settings.


Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 49 ◽  
Author(s):  
Francesca Degrassi ◽  
Michela Damizia ◽  
Patrizia Lavia

Regulators of mitotic division, when dysfunctional or expressed in a deregulated manner (over- or underexpressed) in somatic cells, cause chromosome instability, which is a predisposing condition to cancer that is associated with unrestricted proliferation. Genes encoding mitotic regulators are growingly implicated in neurodevelopmental diseases. Here, we briefly summarize existing knowledge on how microcephaly-related mitotic genes operate in the control of chromosome segregation during mitosis in somatic cells, with a special focus on the role of kinetochore factors. Then, we review evidence implicating mitotic apparatus- and kinetochore-resident factors in the origin of congenital microcephaly. We discuss data emerging from these works, which suggest a critical role of correct mitotic division in controlling neuronal cell proliferation and shaping the architecture of the central nervous system.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sung Hyun Kim ◽  
Mahipal Ganji ◽  
Eugene Kim ◽  
Jaco van der Torre ◽  
Elio Abbondanzieri ◽  
...  

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.


Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 419
Author(s):  
Asia Saorin ◽  
Emanuela Di Gregorio ◽  
Gianmaria Miolo ◽  
Agostino Steffan ◽  
Giuseppe Corona

Ovarian cancer is considered a silent killer due to the lack of clear symptoms and efficient diagnostic tools that often lead to late diagnoses. Over recent years, the impelling need for proficient biomarkers has led researchers to consider metabolomics, an emerging omics science that deals with analyses of the entire set of small-molecules (≤1.5 kDa) present in biological systems. Metabolomics profiles, as a mirror of tumor–host interactions, have been found to be useful for the analysis and identification of specific cancer phenotypes. Cancer may cause significant metabolic alterations to sustain its growth, and metabolomics may highlight this, making it possible to detect cancer in an early phase of development. In the last decade, metabolomics has been widely applied to identify different metabolic signatures to improve ovarian cancer diagnosis. The aim of this review is to update the current status of the metabolomics research for the discovery of new diagnostic metabolomic biomarkers for ovarian cancer. The most promising metabolic alterations are discussed in view of their potential biological implications, underlying the issues that limit their effective clinical translation into ovarian cancer diagnostic tools.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaodan Bai ◽  
Shengyu Hua ◽  
Junping Zhang ◽  
Shixin Xu

An increasing number of research studies over recent years have focused on the function of microRNA (miRNA) molecules which have unique characteristics in terms of structure and function. They represent a class of endogenous noncoding single-strand small molecules. An abundance of miRNA clusters has been found in the genomes of various organisms often located in a polycistron. The miR-17-92 family is among the most famous miRNAs and has been identified as an oncogene. The functions of this cluster, together with the seven individual molecules that it comprises, are most related to cancers, so it would not be surprising that they are considered to have involvement in the development of tumors. The miR-17-92 cluster is therefore expected not only to be a tumor marker, but also to perform an important role in the early diagnosis of those diseases and possibly also be a target for tumor biotherapy. The miR-17-92 cluster affects the development of disease by regulating many related cellular processes and multiple target genes. Interestingly, it also has important roles that cannot be ignored in disease of the nervous system and circulation and modulates the growth and development of bone. Therefore, it provides new opportunities for disease prevention, clinical diagnosis, prognosis, and targeted therapy. Here we review the role of the miR-17-92 cluster that has received little attention in relation to neurological diseases, cardiac diseases, and the development of bone and tumors.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4682
Author(s):  
Judit Liaño-Pons ◽  
Marie Arsenian-Henriksson ◽  
Javier León

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.


2018 ◽  
Vol 5 (2) ◽  
pp. 8-15
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.


2019 ◽  
Vol 133 (24) ◽  
pp. 2481-2498 ◽  
Author(s):  
Hannah E. Morris ◽  
Karla B. Neves ◽  
Augusto C. Montezano ◽  
Margaret R. MacLean ◽  
Rhian M. Touyz

Abstract Notch signalling is critically involved in vascular morphogenesis and function. Four Notch isoforms (Notch1–4) regulating diverse cellular processes have been identified. Of these, Notch3 is expressed almost exclusively in vascular smooth muscle cells (VSMCs), where it is critically involved in vascular development and differentiation. Under pathological conditions, Notch3 regulates VSMC switching between the contractile and synthetic phenotypes. Abnormal Notch3 signalling plays an important role in vascular remodelling, a hallmark of several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Because of the importance of Notch3 in VSMC (de)differentiation, Notch3 has been implicated in the pathophysiology of pulmonary vascular remodelling in PAH. Here we review the current literature on the role of Notch in VSMC function with a focus on Notch3 signalling in pulmonary artery VSMCs, and discuss potential implications in pulmonary artery remodelling in PAH.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Alfred Buhagiar ◽  
Duncan Ayers

Neuroblastoma is a type of cancer that develops most often in infants and children under the age of five years. Neuroblastoma originates within the peripheral sympathetic ganglia, with 30% of the cases developing within the adrenal medulla, although it can also occur within other regions of the body such as nerve tissue in the spinal cord, neck, chest, abdomen, and pelvis. MicroRNAs (miRNAs) regulate cellular pathways, differentiation, apoptosis, and stem cell maintenance. Such miRNAs regulate genes involved in cellular processes. Consequently, they are implicated in the regulation of a spectrum of signaling pathways within the cell. In essence, the role of miRNAs in the development of cancer is of utmost importance for the understanding of dysfunctional cellular pathways that lead to the conversion of normal cells into cancer cells. This review focuses on highlighting the recent, important implications of miRNAs within the context of neuroblastoma basic research efforts, particularly concerning miRNA influences on cancer stem cell pathology and chemoresistance pathology for this condition, together with development of translational medicine approaches for novel diagnostic tools and therapies for this neuroblastoma.


MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Rebecca Mathew ◽  
Valentina Mattei ◽  
Muna Al Hashmi ◽  
Sara Tomei

MicroRNAs are RNA molecules of ~22 nt length that regulate gene expression posttranscriptionally. The role of miRNAs has been reported in many cellular processes including apoptosis, cell differentiation, development and proliferation. The dysregulated expression of miRNAs has been proposed as a biomarker for the diagnosis, onset and prognosis of human diseases. The utility of miRNA profiles to identify and discriminate patients from healthy individuals is highly dependent on the sensitivity and specificity of the technologies used for their detection and the quantity and quality of starting material. In this review, we present an update of the current technologies for the extraction, QC assessment and detection of miRNAs with special focus to the most recent methods, discussing their advantages as well as their shortcomings.


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