scholarly journals Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marco Ragusa ◽  
Cristina Barbagallo ◽  
Duilia Brex ◽  
Angela Caponnetto ◽  
Matilde Cirnigliaro ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Noncoding Rnas ◽  
Special Focus ◽  
Cellular Mechanisms ◽  
Protein Coding ◽  
The Past ◽  
Higher Eukaryotes

Over the past few years, noncoding RNAs (ncRNAs) have been extensively studied because of the significant biological roles that they play in regulation of cellular mechanisms. ncRNAs are associated to higher eukaryotes complexity; accordingly, their dysfunction results in pathological phenotypes, including cancer. To date, most research efforts have been mainly focused on how ncRNAs could modulate the expression of protein-coding genes in pathological phenotypes. However, recent evidence has shown the existence of an unexpected interplay among ncRNAs that strongly influences cancer development and progression. ncRNAs can interact with and regulate each other through various molecular mechanisms generating a complex network including different species of RNAs (e.g., mRNAs, miRNAs, lncRNAs, and circRNAs). Such a hidden network of RNA-RNA competitive interactions pervades and modulates the physiological functioning of canonical protein-coding pathways involved in proliferation, differentiation, and metastasis in cancer. Moreover, the pivotal role of ncRNAs as keystones of network structural integrity makes them very attractive and promising targets for innovative RNA-based therapeutics. In this review we will discuss: (1) the current knowledge on complex crosstalk among ncRNAs, with a special focus on cancer; and (2) the main issues and criticisms concerning ncRNAs targeting in therapeutics.

scholarly journals MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs

2020 ◽  
Vol 21 (6) ◽  
pp. 2229 ◽  
Author(s):  
Monika M. Kaczmarek ◽  
Joanna Najmula ◽  
Maria M. Guzewska ◽  
Emilia Przygrodzka
Keyword(s):  
Current Knowledge ◽  
Mammalian Species ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Large Family ◽  
Protein Coding ◽  
The Past ◽  
Domestic Livestock ◽  
Implantation Period

MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk.

scholarly journals Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma

2017 ◽  
Vol 9 ◽  
pp. 1179299X1773730 ◽  
Author(s):  
Mrigaya Mehra ◽  
Ranjit Chauhan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Structural Integrity ◽  
Gene Expression Regulation ◽  
Noncoding Rnas ◽  
Clinical Applications ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Cellular Processes ◽  
The World

Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non–protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far.

scholarly journals Riddle of the Sphinx: Emerging Role of Transfer RNAs in Human Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhilin Qiu ◽  
Qin Wang ◽  
Lei Liu ◽  
Guozheng Li ◽  
Yi Hao ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Current Knowledge ◽  
Human Cancer ◽  
Special Focus ◽  
Basic Characteristics ◽  
Knowledge Of Cancer ◽  
Cancer Diagnosis And Therapy

The dysregulation of transfer RNA (tRNA) expression contributes to the diversity of proteomics, heterogeneity of cell populations, and instability of the genome, which may be related to human cancer susceptibility. However, the relationship between tRNA dysregulation and cancer susceptibility remains elusive because the landscape of cancer-associated tRNAs has not been portrayed yet. Furthermore, the molecular mechanisms of tRNAs involved in tumorigenesis and cancer progression have not been systematically understood. In this review, we detail current knowledge of cancer-related tRNAs and comprehensively summarize the basic characteristics and functions of these tRNAs, with a special focus on their role and involvement in human cancer. This review bridges the gap between tRNAs and cancer and broadens our understanding of their relationship, thus providing new insights and strategies to improve the potential clinical applications of tRNAs for cancer diagnosis and therapy.

scholarly journals The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 632
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cancer Development ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
The Past ◽  
Cancer Phenotypes ◽  
Coding Potential

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

scholarly journals LncRNAs in Cardiomyocyte Maturation: New Window for Cardiac Regenerative Medicine

2021 ◽  
Vol 7 (1) ◽  
pp. 20
Author(s):  
Maryam Kay ◽  
Bahram M. Soltani
Keyword(s):  
Regenerative Medicine ◽  
Pluripotent Stem Cell ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Maturation Process ◽  
Cell Replacement Therapy ◽  
Cell Replacement ◽  
The Past ◽  
Oligonucleotide Delivery

Cardiomyocyte (CM) maturation, which is characterized by structural, functional, and metabolic specializations, is the last phase of CM development that prepares the cells for efficient and forceful contraction throughout life. Over the past decades, CM maturation has gained increased attention due to the fact that pluripotent stem cell-derived CMs are structurally, transcriptionally, and functionally immature and embryonic-like, which causes a defect in cell replacement therapy. The current challenge is to discover and understand the molecular mechanisms, which control the CM maturation process. Currently, emerging shreds of evidence emphasize the role of long noncoding RNAs (lncRNAs) in regulating different aspects of CM maturation, including myofibril maturation, electrophysiology, and Ca2+ handling maturation, metabolic maturation and proliferation to hypertrophy transition. Here, we describe the structural and functional characteristics of mature CMs. Furthermore, this review highlights the lncRNAs as crucial regulators of different aspects in CM maturation, which have the potential to be used for mature CM production. With the current advances in oligonucleotide delivery; lncRNAs may serve as putative therapeutic targets to produce highly mature CMs for research and regenerative medicine.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

scholarly journals Lipid Transporters Beam Signals from Cell Membranes

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 562
Author(s):  
Miliça Ristovski ◽  
Danny Farhat ◽  
Shelly Ellaine M. Bancud ◽  
Jyh-Yeuan Lee
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Integral Membrane Proteins ◽  
Cellular Membranes ◽  
Cytoplasmic Proteins ◽  
Lipid Transporters

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

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