scholarly journals A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

2018 ◽  
Vol 159 (7) ◽  
pp. 252-259 ◽  
Author(s):  
Kinga Németh ◽  
Ottó Darvasi ◽  
Nikolette Szücs ◽  
Sándor Czirják ◽  
Henriett Butz

Abstract: MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets. Through adjustment of miRNA levels by artificial miRNAs administration or miRNA inhibition, we can influence not only one target gene but also complex biological pathways. Pituitary adenoma is the second most frequent intracranial tumor. In spite of this, the molecular mechanism of the pituitary adenoma formation is not yet entirely revealed. Recently, more and more evidences have been found suggesting that miRNAs have an important role in pituitary adenoma pathogenesis. Here, we summarize the recent results related to this role and highlight the therapeutic potentials in pituitary adenomas. Orv Hetil. 2018; 159(7): 252–259.

2012 ◽  
Vol 287 (15) ◽  
pp. 12405-12416 ◽  
Author(s):  
Tong Zhang ◽  
Jhoanna G. Berrocal ◽  
Jie Yao ◽  
Michelle E. DuMond ◽  
Raga Krishnakumar ◽  
...  

NMNAT-1 and PARP-1, two key enzymes in the NAD+ metabolic pathway, localize to the nucleus where integration of their enzymatic activities has the potential to control a variety of nuclear processes. Using a variety of biochemical, molecular, cell-based, and genomic assays, we show that NMNAT-1 and PARP-1 physically and functionally interact at target gene promoters in MCF-7 cells. Specifically, we show that PARP-1 recruits NMNAT-1 to promoters where it produces NAD+ to support PARP-1 catalytic activity, but also enhances the enzymatic activity of PARP-1 independently of NAD+ production. Furthermore, using two-photon excitation microscopy, we show that NMNAT-1 catalyzes the production of NAD+ in a nuclear pool that may be distinct from other cellular compartments. In expression microarray experiments, depletion of NMNAT-1 or PARP-1 alters the expression of about 200 protein-coding genes each, with about 10% overlap between the two gene sets. NMNAT-1 enzymatic activity is required for PARP-1-dependent poly(ADP-ribosyl)ation at the promoters of commonly regulated target genes, as well as the expression of those target genes. Collectively, our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters.


2020 ◽  
Vol 9 (1) ◽  
pp. 3-13
Author(s):  
Nguyen Hoang Danh ◽  
Thieu Hong Hue ◽  
Quang Trong Minh ◽  
K' Trong Nghia ◽  
Nguyen Thanh Tung ◽  
...  

miRNA (microRNA) are short RNA molecules in length from 20 to 24 nucleotides that have been shown to play an important role in regulating gene expression in many different types of human cancer. Meanwhile, miRNA-214 is one of the known miRNAs involved in the formation of nasopharyngeal carcinoma (NPC) through overexpression that promotes proliferation and development of cancer cells. However, in Vietnam, the study of miR-214 related to NPC has not been conducted yet. With the aims to develop the further studies of miR-214 on NPC in Vietnamese patients, in this initial study, we conducted the analysis of miR-214 expression in previous publications, as well as the prediction of miR-214 potential target genes, which involved in many cellular pathways. Here we applied bioinformatics tools to predict miRNAs and their targets, and discuss the role of miR-214 in the context of human cancers. As the results, miR-214 acted as the oncogenic roles in NPC, relevanted to many pathways, such as cell proliferation, apoptosis, metastasis and invasion through the its target genes LTF, Bim, Bax, LINC0086, etc. In conclusion, the use of computional approaches facilitate the further experimental validation of miRNAs in general, particularly miR-214, in Vietnamese NPC patients.


2020 ◽  
Vol 21 (12) ◽  
pp. 4214 ◽  
Author(s):  
Rossella Gratton ◽  
Paola Maura Tricarico ◽  
Chiara Moltrasio ◽  
Ana Sofia Lima Estevão de Oliveira ◽  
Lucas Brandão ◽  
...  

Notch signaling orchestrates the regulation of cell proliferation, differentiation, migration and apoptosis of epidermal cells by strictly interacting with other cellular pathways. Any disruption of Notch signaling, either due to direct mutations or to an aberrant regulation of genes involved in the signaling route, might lead to both hyper- or hypo-activation of Notch signaling molecules and of target genes, ultimately inducing the onset of skin diseases. The mechanisms through which Notch contributes to the pathogenesis of skin diseases are multiple and still not fully understood. So far, Notch signaling alterations have been reported for five human skin diseases, suggesting the involvement of Notch in their pathogenesis: Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis and Atopic Dermatitis. In this review, we aim at describing the role of Notch signaling in the skin, particularly focusing on the principal consequences associated with its alterations in these five human skin diseases, in order to reorganize the current knowledge and to identify potential cellular mechanisms in common between these pathologies.


2020 ◽  
Vol 21 (19) ◽  
pp. 7287
Author(s):  
Ozal Beylerli ◽  
Narasimha M. Beeraka ◽  
Ilgiz Gareev ◽  
Valentin Pavlov ◽  
Guang Yang ◽  
...  

Pituitary adenoma (PA) accounts for 10–15% of all intracranial neoplasms. Even though most pituitary adenomas are benign, it is known that almost 35% of them exhibit an aggressive clinical course, including rapid proliferative activity and invasion of neighboring tissues. MicroRNAs (miRNAs) are short single-stranded RNA molecules that can influence post-transcriptional regulation by controlling target genes. Based on research data on miRNAs over the past 20 years, more than 60% of genes encoding human proteins are regulated by miRNAs, which ultimately control basic cellular mechanisms, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNAs has been observed in a number of diseases, especially tumors like PA. A majority of miRNAs are expressed within the cells themselves. However, the circulating miRNAs can be detected in several biological fluids of the human body. The identification of circulating miRNAs as new molecular markers may increase the ability to detect a tumor, predict the course of a disease, plan to choose suitable treatment, and diagnose at the earliest signs of impending neoplastic transformation. Therapy of PAs with aggressive behavior is a complex task. When surgery and chemotherapy fail, radiotherapy becomes the treatment of choice against PAs. Therefore, the possibility of implementing circulating miRNAs as innovative diagnostic and therapeutic agents for PA is one of the main exciting ideas.


2020 ◽  
Vol 17 ◽  
Author(s):  
Basit Jabbar ◽  
Batcho Agossa Anicet ◽  
Muhammad Bilal Sarwar ◽  
Bushra Rashid ◽  
Sameera Hassan ◽  
...  

Aim: Exploring molecular mechanism of abiotic stress tolerance in plants is the need to overcome the deterioration of yield and quality of crop plants to meet the food security challenges of growing population. Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate target gene expression for modulating plant growth, development, and response to different stresses. Agave belonging to CAM plants’ has remarkable tolerance to extreme conditions of drought and heat; however, molecular mechanisms underlying this excellence are yet to explore. Objective: This study applies comparative genomics approach on available Transcriptome (RNA-Seq) data of Agave deserti to identify potential miRNAs, and miRNA targets. Methods: Transcriptome datasets consisting of 128,869 Agave contigs processed to create local database, for nucleotide homology analysis with 6,028 non-redundant plant miRNAs as query sequences. Protein coding sequences were removed, and potential pre-miRNA sequences were tested for stability analysis based on a variety of factors, including but not limited to %G+C content and minimum free energy (-∆G), as a filter to remove pseudo pre-miRNAs. Results: This study identified 30 unique miRNAs of Agave deserti harboring 14 different categories of precursors. Phylogenetic analysis revealed evolutionary relationship between newly identified pre-miRNAs with corresponding pre-miRNA homologues. Target genes of miRNAs predicted subsequently, and possible functions defined by functional annotation analysis. Conclusion: The results of this study will pave the way for further research, exploring the molecular mechanisms in Agave deserti and the role of miRNAs in gene regulation under abiotic stresses.


2021 ◽  
Vol 19 (2) ◽  
pp. 145-174
Author(s):  
Petr D. Shabanov ◽  
Vladimir I. Vashchenko

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new preventive and therapeutic strategies for medical treatment viral disease, and СOVID-19.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marco Ragusa ◽  
Cristina Barbagallo ◽  
Duilia Brex ◽  
Angela Caponnetto ◽  
Matilde Cirnigliaro ◽  
...  

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.


2021 ◽  
Author(s):  
Sandrine Lagarrigue ◽  
Matthias Lorthiois ◽  
Fabien Degalez ◽  
David Gilot ◽  
Thomas Derrien

AbstractAnimal genomes are pervasively transcribed into multiple RNA molecules, of which many will not be translated into proteins. One major component of this transcribed non-coding genome is the long non-coding RNAs (lncRNAs), which are defined as transcripts longer than 200 nucleotides with low coding-potential capabilities. Domestic animals constitute a unique resource for studying the genetic and epigenetic basis of phenotypic variations involving protein-coding and non-coding RNAs, such as lncRNAs. This review presents the current knowledge regarding transcriptome-based catalogues of lncRNAs in major domesticated animals (pets and livestock species), covering a broad phylogenetic scale (from dogs to chicken), and in comparison with human and mouse lncRNA catalogues. Furthermore, we describe different methods to extract known or discover novel lncRNAs and explore comparative genomics approaches to strengthen the annotation of lncRNAs. We then detail different strategies contributing to a better understanding of lncRNA functions, from genetic studies such as GWAS to molecular biology experiments and give some case examples in domestic animals. Finally, we discuss the limitations of current lncRNA annotations and suggest research directions to improve them and their functional characterisation.


2021 ◽  
Vol 22 (2) ◽  
pp. 632
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu

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.


2021 ◽  
Vol 22 (10) ◽  
pp. 5087
Author(s):  
Sebastian Gasparis ◽  
Mateusz Przyborowski ◽  
Anna Nadolska-Orczyk

Long noncoding RNAs (lncRNAs) are a class of RNA molecules with gene regulatory functions in plant development and the stress response. Although the number of lncRNAs identified in plants is rapidly increasing, very little is known about their role in barley development. In this study, we performed global identification of barley lncRNAs based on 53 RNAseq libraries derived from nine different barley tissues and organs. In total, 17,250 lncRNAs derived from 10,883 loci were identified, including 8954 novel lncRNAs. Differential expression of lncRNAs was observed in the developing shoot apices and grains, the two organs that have a direct influence on the final yield. The regulatory interaction of differentially expressed lncRNAs with the potential target genes was evaluated. We identified 176 cis-acting lncRNAs in shoot apices and 424 in grains, while the number of trans-acting lncRNAs in these organs was 1736 and 540, respectively. The potential target protein-coding genes were identified, and their biological function was annotated using MapMan ontology. This is the first insight into the roles of lncRNAs in barley development on the genome-wide scale, and our results provide a solid background for future functional studies.


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