RNA 2’-O-Methylation (Nm) Modification in Human Diseases

Nm (2’-O-methylation) is one of the most common modifications in the RNA world. It has the potential to influence the RNA molecules in multiple ways, such as structure, stability, and interactions, and to play a role in various cellular processes from epigenetic gene regulation, through translation to self versus non-self recognition. Yet, building scientific knowledge on the Nm matter has been hampered for a long time by the challenges in detecting and mapping this modification. Today, with the latest advancements in the area, more and more Nm sites are discovered on RNAs (tRNA, rRNA, mRNA, and small non-coding RNA) and linked to normal or pathological conditions. This review aims to synthesize the Nm-associated human diseases known to date and to tackle potential indirect links to some other biological defects.

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MiR-155: An Important Regulator of Neuroinflammation

International Journal of Molecular Sciences ◽

10.3390/ijms23010090 ◽

2021 ◽

Vol 23 (1) ◽

pp. 90

Author(s):

Valeria Domenica Zingale ◽

Agnese Gugliandolo ◽

Emanuela Mazzon

Keyword(s):

Neurological Diseases ◽

Transcriptional Level ◽

Regulate Gene Expression ◽

Rna Molecules ◽

Cellular Processes ◽

Non Coding Rna ◽

Important Regulator ◽

The Central Nervous System ◽

High Concentrations ◽

Mirnas Expression

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.

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(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

Cancers ◽

10.3390/cancers13205040 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5040

Author(s):

Maja Sabol ◽

Jean Calleja-Agius ◽

Riccardo Di Di Fiore ◽

Sherif Suleiman ◽

Sureyya Ozcan ◽

...

Keyword(s):

Posttranslational Modifications ◽

Tumor Development ◽

Gene Mutations ◽

Delay In Diagnosis ◽

Rna Molecules ◽

Cellular Processes ◽

Ovarian Cancers ◽

Non Coding Rna ◽

Underlying Causes ◽

Low Incidence

Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women of all ages, but due to their low incidence and the potential clinical inexperience in management, there can be a delay in diagnosis, leading to a poor prognosis. The underlying causes for these tumors are varied, but generally, the tumors arise due to alterations in gene/protein expression in cellular processes that regulate normal proliferation and its checkpoints. Dysregulation of the cellular processes that lead to cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional and posttranslational modifications. Long non-coding RNA (lncRNA) are defined as transcribed RNA molecules, more than 200 nucleotides in length which are not translated into proteins. They regulate gene expression through several mechanisms and therefore add another level of complexity to the regulatory mechanisms affecting tumor development. Since few studies have been performed on ROCs, in this review we summarize the mechanisms of action of lncRNA in OC, with an emphasis on ROCs.

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MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications

Non-Coding RNA ◽

10.3390/ncrna5020035 ◽

2019 ◽

Vol 5 (2) ◽

pp. 35 ◽

Cited By ~ 42

Author(s):

Slota ◽

Booth

Keyword(s):

Biomarker Discovery ◽

Prion Diseases ◽

Herpes Encephalitis ◽

Inflammatory Signaling ◽

Ongoing Research ◽

Rna Molecules ◽

Cellular Processes ◽

Non Coding Rna ◽

The Central Nervous System ◽

Mirna Deregulation

The central nervous system can respond to threat via the induction of an inflammatory response. Under normal circumstances this response is tightly controlled, however uncontrolled neuroinflammation is a hallmark of many neurological disorders. MicroRNAs are small non-coding RNA molecules that are important for regulating many cellular processes. The ability of microRNAs to modulate inflammatory signaling is an area of ongoing research, which has gained much attention in recent years. MicroRNAs may either promote or restrict inflammatory signaling, and either exacerbate or ameliorate the pathological consequences of excessive neuroinflammation. The aim of this review is to summarize the mode of regulation for several important and well-studied microRNAs in the context of neuroinflammation, including miR-155, miR-146a, miR-124, miR-21 and let-7. Furthermore, the pathological consequences of miRNA deregulation during disorders that feature neuroinflammation are discussed, including Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease, Prion diseases, Japanese encephalitis, Herpes encephalitis, ischemic stroke and traumatic brain injury. There has also been considerable interest in the use of altered microRNA signatures as biomarkers for these disorders. The ability to modulate microRNA expression may even serve as the basis for future therapeutic strategies to help treat pathological neuroinflammation.

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Role of microRNAs in neuroendocrine neoplasms of the stomach

Advances in molecular oncology ◽

10.17650/2313-805x-2020-7-3-19-26 ◽

2020 ◽

Vol 7 (3) ◽

pp. 19-26

Author(s):

I. N. Peregorodiev ◽

S. V. Vinokurova ◽

V. Yu. Bohyan ◽

V. V. Delektorskaya ◽

O. A. Malikhova ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Neuroendocrine Tumors ◽

Malignant Tumors ◽

Large Cell ◽

Microrna Expression ◽

Neuroendocrine Neoplasms ◽

Rna Molecules ◽

Cellular Processes ◽

Non Coding Rna

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare epithelial tumors that arise from cells with a neuroendocrine phenotype. NENs are found in the gastrointestinal tract and pancreas – 60 % of all localities. The incidence of gastric NENs is about 9 % of all neuroendocrine tumors of the gastrointestinal tract and 0.3 % of all stomach tumors. Stomach neuroendocrine tumors (NETs) are classified into three clinico-pathological types, based on etiology, pathogenesis and morphology. There are also separate neuroendocrine cancers: small- and large-cell. The prognosis and approach to treatment of various types of gastric NENs differs significantly. Modern methods of instrumental diagnostics, immunohistochemical methods of morphological research, along with light microscopy, do not always allow us to accurately assess the malignant potential of a tumor and individualize the treatment process. One of the promising directions in the study of NETs is to determine the molecular mechanism underlying their development, in particular the role of microRNAs. This direction can open a new vector of understanding the pathogenesis, determining the prognosis of the disease, as well as finding new application points for the drug treatment of NETs. MicroRNAs are a class of short non-coding RNA molecules (18–25 nucleotides). MicroRNAs can be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. A study of microRNA expression in tissues revealed tumor-specific microRNAs. In contrast to a number of other malignant tumors, microRNA expression in patients diagnosed with NENs is poorly understood. MicroRNA-222 and microRNA-202 are among the few microRNAs that have been demonstrated in the NETs of the stomach.

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It's an RNA world: a focus on recent advances in RNA biochemistry

The Biochemist ◽

10.1042/bio03802004 ◽

2016 ◽

Vol 38 (2) ◽

pp. 4-7

Author(s):

Sheila Graham

Keyword(s):

Molecular Biology ◽

Protein Interactions ◽

Rna World ◽

Enzymatic Catalysis ◽

Protein Translation ◽

Rna Molecules ◽

The Core ◽

Recent Advances ◽

Non Coding Rna ◽

Encoding Protein

RNA is a fascinating molecule. Its array of different properties is highlighted by our knowledge of the ribosome. RNA can have structural properties; for example, rRNA is the core of the ribosome. RNA can bind proteins; for example, rRNA–ribosomal protein interactions are used to build the protein translation machinery. Finally, RNA can display enzymatic catalysis. In the ribosome during translation, non-coding RNA carries out decoding (tRNA) and amino acid polymerization (rRNA). If this is not fascinating enough, the last decade or so has seen a considerable reassessment of the core of Francis Crick's ‘central dogma of molecular biology’ that states that RNA molecules (rRNAs, tRNAs and mRNAs) serve to drive protein synthesis, decode mRNAs or act as a templates encoding protein. Much of the upheaval in our understanding of RNA biology has come from deep mining of the human transcriptome by RNA sequencing (RNAseq) by next generation sequencing techniques. One of the most startling revelations from the wealth of new data provided by the ‘-omics’ revolution is that over 80% of the human genome encodes RNA, whereas only up to 2% encodes proteins. In other words, our genomes are largely RNA-coding. The discovery of the plethora of non-coding RNAs in our genomes has revolutionized molecular biology. These RNAs do not encode protein and, unlike rRNAs or tRNAs, most are not intimately linked to protein translation. In this edition of The Biochemist, we revisit recent advances in RNA research to reveal the broad scope of this hot topic in today's biochemistry and to spotlight some new areas of RNA research.

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MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy

Cardiovascular Diabetology ◽

10.1186/s12933-020-01107-3 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Karima Ait-Aissa ◽

Quynh My Nguyen ◽

Mohanad Gabani ◽

Adam Kassan ◽

Santosh Kumar ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Therapeutic Potential ◽

Sirtuin 1 ◽

Molecular Therapy ◽

Rna Molecules ◽

Global Epidemic ◽

Cellular Processes ◽

Non Coding Rna ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Abstract The endothelium plays a pivotal role in maintaining vascular health. Obesity is a global epidemic that has seen dramatic increases in both adult and pediatric populations. Obesity perturbs the integrity of normal endothelium, leading to endothelial dysfunction which predisposes the patient to cardiovascular diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNA molecules that play important roles in a variety of cellular processes such as differentiation, proliferation, apoptosis, and stress response; their alteration contributes to the development of many pathologies including obesity. Mediators of obesity-induced endothelial dysfunction include altered endothelial nitric oxide synthase (eNOS), Sirtuin 1 (SIRT1), oxidative stress, autophagy machinery and endoplasmic reticulum (ER) stress. All of these factors have been shown to be either directly or indirectly caused by gene regulatory mechanisms of miRNAs. In this review, we aim to provide a comprehensive description of the therapeutic potential of miRNAs to treat obesity-induced endothelial dysfunction. This may lead to the identification of new targets for interventions that may prevent or delay the development of obesity-related cardiovascular disease.

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Role of microRNAs in the molecular diagnosis of cancer

Journal of Nucleic Acids Investigation ◽

10.4081/jnai.2010.1659 ◽

2010 ◽

Vol 1 (1) ◽

pp. 4 ◽

Cited By ~ 4

Author(s):

Simona Giglio ◽

Andrea Vecchione

Keyword(s):

Unknown Origin ◽

Rna Molecules ◽

Cellular Processes ◽

Non Coding Rna ◽

Evolutionarily Conserved ◽

Diagnosis Of Cancer ◽

Diagnosis And Classification ◽

Tumor Types ◽

Cycle Regulation

MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, small non-coding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are involved in numerous cellular processes including development, cell differentiation, cell cycle regulation and apoptosis. There is increasing evidence to show that miRNAs are mutated or differentially expressed in many types of cancer and specific functions of the miRNAs are now becoming apparent. Here we discuss the current literature on potential usefulness of miRNAs as diagnostic markers, emphasizing the involvement of specific miRNAs in particular tumor types, highlighting their potential role in distinguishing benign from malignant tissues and/or the different subtypes of the same tumor and/or in diagnosis and classification of tumor of unknown origin.

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Recent Advances on the Semi-Supervised Learning for Long Non-Coding RNA-Protein Interactions Prediction: A Review

Protein and Peptide Letters ◽

10.2174/0929866526666191025104043 ◽

2020 ◽

Vol 27 (5) ◽

pp. 385-391

Author(s):

Lin Zhong ◽

Zhong Ming ◽

Guobo Xie ◽

Chunlong Fan ◽

Xue Piao

Keyword(s):

Supervised Learning ◽

Protein Interactions ◽

Computational Models ◽

Prediction Models ◽

Chromatin Modification ◽

Computational Prediction ◽

Human Diseases ◽

Future Research ◽

Non Coding Rna ◽

Long Non Coding Rna

: In recent years, more and more evidence indicates that long non-coding RNA (lncRNA) plays a significant role in the development of complex biological processes, especially in RNA progressing, chromatin modification, and cell differentiation, as well as many other processes. Surprisingly, lncRNA has an inseparable relationship with human diseases such as cancer. Therefore, only by knowing more about the function of lncRNA can we better solve the problems of human diseases. However, lncRNAs need to bind to proteins to perform their biomedical functions. So we can reveal the lncRNA function by studying the relationship between lncRNA and protein. But due to the limitations of traditional experiments, researchers often use computational prediction models to predict lncRNA protein interactions. In this review, we summarize several computational models of the lncRNA protein interactions prediction base on semi-supervised learning during the past two years, and introduce their advantages and shortcomings briefly. Finally, the future research directions of lncRNA protein interaction prediction are pointed out.

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Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

Journal of Personalized Medicine ◽

10.3390/jpm11060513 ◽

2021 ◽

Vol 11 (6) ◽

pp. 513

Author(s):

Zheng Zhang ◽

Meng Gu ◽

Zhongze Gu ◽

Yan-Ru Lou

Keyword(s):

Molecular Mechanisms ◽

Neurological Diseases ◽

Cellular Processes ◽

Dna And Rna ◽

Chemotherapeutic Response ◽

Non Coding Rna ◽

Response To Chemotherapy ◽

Personalized Oncology ◽

Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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