scholarly journals MicroRNAs: crucial regulators of placental development

Reproduction ◽  
2018 ◽  
Vol 155 (6) ◽  
pp. R259-R271 ◽  
Author(s):  
Heyam Hayder ◽  
Jacob O’Brien ◽  
Uzma Nadeem ◽  
Chun Peng
Keyword(s):  
Mrna Stability ◽  
Target Genes ◽  
Current Knowledge ◽  
Mirna Biogenesis ◽  
Placental Development ◽  
Future Directions ◽  
Cellular Processes ◽  
Wide Range ◽  
Canonical Pathways

MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that are integral to a wide range of cellular processes mainly through the regulation of translation and mRNA stability of their target genes. The placenta is a transient organ that exists throughout gestation in mammals, facilitating nutrient and gas exchange and waste removal between the mother and the fetus. miRNAs are expressed in the placenta, and many studies have shown that miRNAs play an important role in regulating trophoblast differentiation, migration, invasion, proliferation, apoptosis, vasculogenesis/angiogenesis and cellular metabolism. In this review, we provide a brief overview of canonical and non-canonical pathways of miRNA biogenesis and mechanisms of miRNA actions. We highlight the current knowledge of the role of miRNAs in placental development. Finally, we point out several limitations of the current research and suggest future directions.

scholarly journals Complexity in regulating microRNA biogenesis in cancer

2020 ◽  
Vol 245 (5) ◽  
pp. 395-401
Author(s):  
Pai-Sheng Chen ◽  
Shao-Chieh Lin ◽  
Shaw-Jenq Tsai
Keyword(s):  
Noncoding Rna ◽  
Target Genes ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Cellular Processes ◽  
Wide Range ◽  
Mirnas Expression ◽  
Cellular Phenotypes ◽  
Fine Tune ◽  
Processing Factors

The discovery of microRNA (miRNA) significantly extends our knowledge on gene regulation and noncoding gene functions. MiRNAs are important post-transcriptional regulators involve in a wide range of biological functions and diseases, including cancer. MiRNAs are produced by a unique biogenesis pathway involving the two-step sequential nuclear and cytoplasmic RNase-dependent processing at post-transcriptional level. However, a specific (set) of miRNA(s) is (are) synthesized under certain circumstance or developmental/pathological stage to fine-tune the gene expression profile. In this minireview, we will discuss the mechanism of miRNA biogenesis in cancer, mainly focusing on how Drosha and Dicer, two critical molecules controlling miRNA biogenesis, are modulated and which factor contributes to the specificity of selected miRNA maturation. Impact statement The canonical maturation pathway of miRNAs is highly conserved, indicating the crucial roles of these mini-regulators in most cellular processes. Dysregulation of specific miRNAs or imbalance of miRNA abundance has been observed in cancers. Accumulating evidence has shown that the interplay between miRNA processing factors and regulatory proteins previously known as key players in cancer malignancy regulates the biogenesis of miRNAs, expression of target genes, and eventually the alteration of cellular phenotypes. This minireview summarizes the current findings in the modulation of miRNA biogenesis in cancer to advance the understanding of how noncoding RNA contributes to cancer development and malignancy.

scholarly journals Regulation of peroxisomal trafficking and distribution

2020 ◽  
Author(s):  
Christian Covill-Cooke ◽  
Viktoriya S. Toncheva ◽  
Josef T. Kittler
Keyword(s):  
Rho Gtpases ◽  
Mammalian Cells ◽  
Short Range ◽  
Current Knowledge ◽  
Current Understanding ◽  
Regulatory Mechanisms ◽  
Future Directions ◽  
Contact Sites ◽  
Wide Range

Abstract Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be transported by both long- and short-range trafficking events in response to cellular needs. Here, we review our current understanding of the mechanisms by which the cytoskeleton and organelle contact sites alter peroxisomal distribution. Though the focus of the review is peroxisomal transport in mammalian cells, findings from flies and fungi are used for comparison and to inform the gaps in our understanding. Attention is given to the apparent overlap in regulatory mechanisms for mitochondrial and peroxisomal trafficking, along with the recently discovered role of the mitochondrial Rho-GTPases, Miro, in peroxisomal dynamics. Moreover, we outline and discuss the known pathological and pharmacological conditions that perturb peroxisomal positioning. We conclude by highlighting several gaps in our current knowledge and suggest future directions that require attention.

scholarly journals RFX1: a promising therapeutic arsenal against cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joby Issac ◽  
Pooja S. Raveendran ◽  
Ani V. Das
Keyword(s):  
Protein Interactions ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Protein Protein Interactions ◽  
Oncogenic Potential ◽  
Cellular Processes ◽  
Wide Range ◽  
Induced Apoptosis ◽  
Pleiotropic Function

AbstractRegulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein–protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.

scholarly journals Autophagic degradation of peroxisomes in mammals

2016 ◽  
Vol 44 (2) ◽  
pp. 431-440 ◽  
Author(s):  
Katarzyna Zientara-Rytter ◽  
Suresh Subramani
Keyword(s):  
Mammalian Cells ◽  
Environmental Changes ◽  
Cell Function ◽  
Current Knowledge ◽  
Future Directions ◽  
Cellular Processes ◽  
Wide Range ◽  
Efficient Control ◽  
Autophagic Degradation ◽  
Eukaryotic Organisms

Peroxisomes are essential organelles required for proper cell function in all eukaryotic organisms. They participate in a wide range of cellular processes including the metabolism of lipids and generation, as well as detoxification, of hydrogen peroxide (H2O2). Therefore, peroxisome homoeostasis, manifested by the precise and efficient control of peroxisome number and functionality, must be tightly regulated in response to environmental changes. Due to the existence of many physiological disorders and diseases associated with peroxisome homoeostasis imbalance, the dynamics of peroxisomes have been widely examined. The increasing volume of reports demonstrating significant involvement of the autophagy machinery in peroxisome removal leads us to summarize current knowledge of peroxisome degradation in mammalian cells. In this review we present current models of peroxisome degradation. We particularly focus on pexophagy–the selective clearance of peroxisomes through autophagy. We also critically discuss concepts of peroxisome recognition for pexophagy, including signalling and selectivity factors. Finally, we present examples of the pathological effects of pexophagy dysfunction and suggest promising future directions.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals The Fourth IOCDC

CNS Spectrums ◽  
2000 ◽  
Vol 5 (S4) ◽  
pp. 4-4
Author(s):  
Eric Hollander ◽  
Joseph Zohar ◽  
Donatella Marazziti
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Current Knowledge ◽  
Active Role ◽  
Cortical Inhibition ◽  
Obsessive Compulsive ◽  
Future Directions ◽  
Compulsive Disorder ◽  
Ablative Surgery

The Fourth International Obsessive Compulsive Disorder Conference (IOCDC) was held February 10–12, 2000, on the beautiful island of St. Thomas. The IOCDC is an annual meeting which brings together the world's leading experts in obsessive-compulsive disorder (OCD) and related disorders in a small workshop setting to present recent research advances, discuss gaps in our current knowledge, and plan or international approaches that address these knowledge gaps. The IOCDC meetings have been held on islands on both sides of the Atlantic—Capri, Guadeloupe, Madeira, and now St. Thomas.The International Organizing Committee consists of Eric Hollander, MD (USA), Joseph Zohar, MD (Israel), and Donatella Marazziti, MD (Italy). The proceedings are generously supported by an unrestricted educational grant from Solvay Pharmaceuticals Inc. and Solvay Pharmaceuticals, and we would like to acknowledge the very important contributions of Chantal Vekens and Mary Blangiardo of Solvay. Also, an mportant part of the success of these meetings stems from the very active role of the chairpersons and cochairpersons of the workshops who lead the discussions, who synthesize the future directions and prepare the manuscripts that result from these discussions that appear in this academic supplement.The meeting led off with a state-of-the-art plenary address by Mark George, MD (USA), describing how new methods of brain stimulation are improving research and therapy in OCD and promise to revolutionize neuropsychiatric research and herapy over the next decade. He describes how transcranial magnetic stimulation (TMS) is used to test the circuits in OCD and test electrophysiologic evaluations of cortical inhibition n OCD. Newer techniques that are less invasive than ablative surgery and appear promising in OCD therapy include vagus nerve stimulation and deep brain stimulation.

The role of hypoxia in endometrial cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Yarely M. Salinas-Vera ◽  
Dolores Gallardo-Rincón ◽  
Erika Ruíz-García ◽  
Macrina B. Silva-Cázares ◽  
Carmen Sol de la Peña-Cruz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Vasculogenic Mimicry ◽  
Cellular Processes ◽  
Corpus Uteri

: Endometrial cancer represents the most frequent neoplasia from the corpus uteri, and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance urged to ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors from breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

scholarly journals Autophagy is activated in the ovarian tissue of polycystic ovary syndrome

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Da Li ◽  
Yue You ◽  
Fang-Fang Bi ◽  
Tie-Ning Zhang ◽  
Jiao Jiao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Potential Role ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Ovary Syndrome ◽  
Cellular Processes ◽  
Transmission Electron ◽  
Wide Range ◽  
Response To Stress

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1, TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

scholarly journals The role of airborne volcanic ash for the surface ocean biogeochemical iron-cycle: a review

2009 ◽  
Vol 6 (4) ◽  
pp. 6441-6489 ◽  
Author(s):  
S. Duggen ◽  
N. Olgun ◽  
P. Croot ◽  
L. Hoffmann ◽  
H. Dietze ◽  
...  
Keyword(s):  
Large Scale ◽  
Volcanic Ash ◽  
Volcanic Eruptions ◽  
Research Field ◽  
Ash Deposition ◽  
Future Directions ◽  
Iron Cycle ◽  
Surface Ocean ◽  
Wide Range

Abstract. Iron is a key micronutrient for phytoplankton growth in the surface ocean. Yet the significance of volcanism for the marine biogeochemical iron-cycle is poorly constrained. Recent studies, however, suggest that offshore deposition of airborne ash from volcanic eruptions is a way to inject significant amounts of bio-available iron into the surface ocean. Volcanic ash may be transported up to several tens of kilometres high into the atmosphere during large-scale eruptions and fine ash may encircle the globe for years, thereby reaching even the remotest and most iron-starved oceanic areas. Scientific ocean drilling demonstrates that volcanic ash layers and dispersed ash particles are frequently found in marine sediments and that therefore volcanic ash deposition and iron-injection into the oceans took place throughout much of the Earth's history. The data from geochemical and biological experiments, natural evidence and satellite techniques now available suggest that volcanic ash is a so far underestimated source for iron in the surface ocean, possibly of similar importance as aeolian dust. Here we summarise the development of and the knowledge in this fairly young research field. The paper covers a wide range of chemical and biological issues and we make recommendations for future directions in these areas. The review paper may thus be helpful to improve our understanding of the role of volcanic ash for the marine biogeochemical iron-cycle, marine primary productivity and the ocean-atmosphere exchange of CO2 and other gases relevant for climate throughout the Earth's history.

scholarly journals Role of the PE/PPE Family in Host–Pathogen Interactions and Prospects for Anti-Tuberculosis Vaccine and Diagnostic Tool Design

2020 ◽  
Vol 10 ◽  
Author(s):  
Jianing Qian ◽  
Run Chen ◽  
Honghai Wang ◽  
Xuelian Zhang
Keyword(s):  
Cell Fate ◽  
Current Knowledge ◽  
Cell Interaction ◽  
Key Factors ◽  
Host Pathogen Interactions ◽  
Future Directions ◽  
Host Pathogen ◽  
Protein Research ◽  
Slow Growing

The pe/ppe genes are found in pathogenic, slow-growing Mycobacterium tuberculosis and other M. tuberculosis complex (MTBC) species. These genes are considered key factors in host-pathogen interactions. Although the function of most PE/PPE family proteins remains unclear, accumulating evidence suggests that this family is involved in M. tuberculosis infection. Here, we review the role of PE/PPE proteins, which are believed to be linked to the ESX system function. Further, we highlight the reported functions of PE/PPE proteins, including their roles in host cell interaction, immune response regulation, and cell fate determination during complex host-pathogen processes. Finally, we propose future directions for PE/PPE protein research and consider how the current knowledge might be applied to design more specific diagnostics and effective vaccines for global tuberculosis control.

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