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1.
Methods Mol Biol ; 2404: 3-41, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34694601

RESUMO

Untranslated regions of mRNA (UTRs) are involved in defining the fate of the transcript through processes such as mRNA localization, degradation, translation initiation regulation, and several others: the action of trans-factors such as RNA-binding proteins and non-coding RNAs, combined with the presence of defined sequence and structural cis-elements, ultimately determines protein synthesis levels. Identifying functional regions in UTRs and uncovering post-transcriptional regulators acting upon these is thus of paramount importance to understand this regulatory layer: these tasks can now be approached computationally to reduce the testable hypothesis space and drive the experimental validation in a more effective way.This chapter will focus on presenting databases and tools allowing to study the various aspects of post-transcriptional regulation, including the profiling of actively translated mRNAs, regulatory network analysis (e.g., RBP and ncRNA binding sites), trans-factor binding sites prediction, motif search (sequence and secondary structure), and other aspects of this regulatory layer: two potential analysis pipelines are also presented as practical examples of how these tools could be integrated and effectively employed.


Assuntos
Biologia Computacional , Regulação da Expressão Gênica , RNA Mensageiro/genética , RNA não Traduzido , Transcrição Genética , Regiões não Traduzidas
2.
J Biomed Sci ; 28(1): 78, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794432

RESUMO

The discovery of various noncoding RNAs (ncRNAs) and their biological implications is a growing area in cell biology. Increasing evidence has revealed canonical and noncanonical functions of long and small ncRNAs, including microRNAs, long ncRNAs (lncRNAs), circular RNAs, PIWI-interacting RNAs, and tRNA-derived fragments. These ncRNAs have the ability to regulate gene expression and modify metabolic pathways. Thus, they may have important roles as diagnostic biomarkers or therapeutic targets in various diseases, including neurodegenerative disorders, especially Parkinson's disease. Recently, through diverse sequencing technologies and a wide variety of bioinformatic analytical tools, such as reverse transcriptase quantitative PCR, microarrays, next-generation sequencing and long-read sequencing, numerous ncRNAs have been shown to be associated with neurodegenerative disorders, including Parkinson's disease. In this review article, we will first introduce the biogenesis of different ncRNAs, including microRNAs, PIWI-interacting RNAs, circular RNAs, long noncoding RNAs, and tRNA-derived fragments. The pros and cons of the detection platforms of ncRNAs and the reproducibility of bioinformatic analytical tools will be discussed in the second part. Finally, the recent discovery of numerous PD-associated ncRNAs and their association with the diagnosis and pathophysiology of PD are reviewed, and microRNAs and long ncRNAs that are transported by exosomes in biofluids are particularly emphasized.


Assuntos
Biomarcadores/metabolismo , Doença de Parkinson/genética , RNA não Traduzido/genética , Animais , Modelos Animais de Doenças , Humanos , Camundongos , RNA não Traduzido/metabolismo
3.
Cells ; 10(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34685492

RESUMO

The ability of the ribonucleic acid (RNA) to self-replicate, combined with a unique cocktail of chemical properties, suggested the existence of an RNA world at the origin of life. Nowadays, this hypothesis is supported by innovative high-throughput and biochemical approaches, which definitively revealed the essential contribution of RNA-mediated mechanisms to the regulation of fundamental processes of life. With the recent development of SARS-CoV-2 mRNA-based vaccines, the potential of RNA as a therapeutic tool has received public attention. Due to its intrinsic single-stranded nature and the ease with which it is synthesized in vitro, RNA indeed represents the most suitable tool for the development of drugs encompassing every type of human pathology. The maximum effectiveness and biochemical versatility is achieved in the guise of non-coding RNAs (ncRNAs), which are emerging as multifaceted regulators of tissue specification and homeostasis. Here, we report examples of coding and ncRNAs involved in muscle regeneration and discuss their potential as therapeutic tools. Small ncRNAs, such as miRNA and siRNA, have been successfully applied in the treatment of several diseases. The use of longer molecules, such as lncRNA and circRNA, is less advanced. However, based on the peculiar properties discussed below, they represent an innovative pool of RNA biomarkers and possible targets of clinical value.


Assuntos
MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , RNA Mensageiro/metabolismo , RNA não Traduzido/genética , Regeneração , Animais , Biomarcadores/metabolismo , COVID-19 , Homeostase , Humanos , Camundongos , Músculo Esquelético/virologia , Miocárdio/metabolismo , Origem da Vida , RNA Circular , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Pequeno RNA não Traduzido/genética , RNA Viral/metabolismo , SARS-CoV-2/genética
4.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638636

RESUMO

RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases. In recent decades, considerable efforts have been devoted to the characterization of noncoding RNAs (ncRNAs) and to the study of their role in the homeostasis of the nervous system (NS), where they are highly enriched. Acting as major regulators of gene expression, ncRNAs orchestrate all the steps of the differentiation programs, participate in the mechanisms underlying neural functions, and are crucially implicated in the development of neuronal pathologies, among which are neurodegenerative diseases. This review aims to explore the link between ncRNA dysregulation and amyotrophic lateral sclerosis (ALS), the most frequent motoneuron (MN) disorder in adults. Notably, defective RNA metabolism is known to be largely associated with this pathology, which is often regarded as an RNA disease. We also discuss the potential role that these transcripts may play as diagnostic biomarkers and therapeutic targets.


Assuntos
Esclerose Amiotrófica Lateral/genética , RNA não Traduzido/genética , Animais , Humanos , Neurônios Motores/patologia , Doenças Neurodegenerativas/genética
5.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638651

RESUMO

The telomeric transcriptome of Chironomus riparius has been involved in thermal stress response. One of the telomeric transcripts, the so-called CriTER-A variant, is highly overexpressed upon heat shock. On the other hand, its homologous variant CriTER-B, which is the most frequently encoded noncoding RNA in the telomeres of C. riparius, is only slightly affected by thermal stress. Interestingly, both transcripts show high sequence homology, but less is known about their folding and how this could influence their differential behaviour. Our study suggests that CriTER-A folds as two different conformers, whose relative proportion is influenced by temperature conditions. Meanwhile, the CriTER-B variant shows only one dominant conformer. Thus, a temperature-dependent conformational equilibrium can be established for CriTER-A, suggesting a putative functional role of the telomeric transcriptome in relation to thermal stress that could rely on the structure-function relationship of the CriTER-A transcripts.


Assuntos
Chironomidae/genética , RNA não Traduzido/genética , Telômero/genética , Transcriptoma/genética , Animais , Sequência de Bases , Resposta ao Choque Térmico/genética , Temperatura Alta
6.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638849

RESUMO

Accurate inference of the relationship between non-coding RNAs (ncRNAs) and drug resistance is essential for understanding the complicated mechanisms of drug actions and clinical treatment. Traditional biological experiments are time-consuming, laborious, and minor in scale. Although several databases provide relevant resources, computational method for predicting this type of association has not yet been developed. In this paper, we leverage the verified association data of ncRNA and drug resistance to construct a bipartite graph and then develop a linear residual graph convolution approach for predicting associations between non-coding RNA and drug resistance (LRGCPND) without introducing or defining additional data. LRGCPND first aggregates the potential features of neighboring nodes per graph convolutional layer. Next, we transform the information between layers through a linear function. Eventually, LRGCPND unites the embedding representations of each layer to complete the prediction. Results of comparison experiments demonstrate that LRGCPND has more reliable performance than seven other state-of-the-art approaches with an average AUC value of 0.8987. Case studies illustrate that LRGCPND is an effective tool for inferring the associations between ncRNA and drug resistance.


Assuntos
Algoritmos , Biologia Computacional/métodos , Resistência a Medicamentos/genética , Modelos Teóricos , RNA não Traduzido/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , MicroRNAs/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
7.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638805

RESUMO

Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare malignant forms have been described. They are heterogeneous in terms of clinical presentation and the associated signs and symptoms overlap with those of disease and aging. Furthermore, most patients with hypercalcemia are discovered during routine blood tests for other reasons. Surgical removal is considered the main therapeutic option to cure these endocrine tumors and, therefore, innovative therapeutic approaches are actively required. Recently, a growing number of studies have suggested that alterations to the epigenetic mechanisms could play a pivotal role in parathyroid tumorigenesis. Most of the attention has been focused on non-coding RNAs (ncRNAs) (i.e., miRNAs, lncRNAs, and circRNAs) whose expression profile has been found to be deregulated in parathyroid tumors. The aim of the present paper is to give an insight into the ncRNAs involved in parathyroid tumorigenesis, which could be used in the future either as innovative diagnostic biomarkers or as therapeutic targets for the treatment of this endocrine neoplasia.


Assuntos
Neoplasias das Paratireoides/metabolismo , RNA não Traduzido/análise , Biomarcadores Tumorais/análise , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , RNA Circular , RNA Longo não Codificante , RNA não Traduzido/metabolismo
8.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638966

RESUMO

Bacterial non-coding RNAs (ncRNAs) play important regulatory roles in various physiological metabolic pathways. In this study, a novel ncRNA CsiR (ciprofloxacin stress-induced ncRNA) involved in the regulation of ciprofloxacin resistance in the foodborne multidrug-resistant Proteus vulgaris (P. vulgaris) strain P3M was identified. The survival rate of the CsiR-deficient strain was higher than that of the wild-type strain P3M under the ciprofloxacin treatment condition, indicating that CsiR played a negative regulatory role, and its target gene emrB was identified through further target prediction, quantitative real-time PCR (qRT-PCR), and microscale thermophoresis (MST). Further studies showed that the interaction between CsiR and emrB mRNA affected the stability of the latter at the post-transcriptional level to a large degree, and ultimately affected the ciprofloxacin resistance of P3M. Notably, the base-pairing sites between CsiR and emrB mRNAs were highly conserved in other sequenced P. vulgaris strains, suggesting that this regulatory mechanism may be ubiquitous in this species. To the best of our knowledge, this is the first identification of a novel ncRNA involved in the regulation of ciprofloxacin resistance in P. vulgaris species, which lays a solid foundation for comprehensively expounding the antibiotic resistance mechanism of P. vulgaris.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Membrana/metabolismo , Proteus vulgaris/efeitos dos fármacos , Proteus vulgaris/metabolismo , RNA não Traduzido/metabolismo , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana/genética , Organismos Geneticamente Modificados , Proteus vulgaris/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1680-1684, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627462

RESUMO

Some non-coding RNAs (ncRNA), as functional RNA molecules, lack potential to encode proteins, but can affect gene expression and disease progression through a variety of mechanisms. In multiple myeloma (MM), cardiovascular disease is one of the most common complications, which may be related to a variety of factors, including patient's own factors, disease-related factors, drug factors, etc. Non-coding RNA is considered to be an important regulator of cardiovascular event risk factors and cell function, and an important candidate target for improving the condition and prognostic assessment. This article briefly summarized the role of non-coding RNA in cardiac amyloidosis caused by MM, damage to the heart by inflammatory factors, and heart disease caused by chemotherapy drugs in recent years.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Prognóstico , RNA não Traduzido/genética
10.
BMC Genomics ; 22(1): 749, 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657595

RESUMO

BACKGROUND: Bovine milk contains extracellular vesicles (EVs) that play a role in cellular communication, acting in either an autocrine, paracrine, or an exocrine manner. The unique properties of the EVs protect the cargo against degradation. We profiled the ncRNAs (non-coding RNA) present in the EVs from seven dairy products - raw whole milk, heat-treated skim milk, homogenized heat-treated skim milk, pasteurized homogenized skim milk, pasteurized heavy whipping cream, sweet cream buttermilk and cultured buttermilk with four replicates each, obtained at different processing steps from a commercial dairy plant. EVs and their cargo were extracted by using a validated commercial kit that has been shown to be efficient and specific for EVs. Further, to find the annotation of ncRNAs, we probed bovine and other organism repositories(such as miRBase, miRTarBase, Ensemble) to find homolog ncRNA annotation in case the annotations of ncRNA are not available in Bos Taurus database. RESULTS: Specifically, 30 microRNAs (miRNAs), were isolated throughout all the seven milk samples, which later when annotated with their corresponding 1546 putative gene targets have functions associated with immune response and growth and development. This indicates the potential for these ncRNAs to beneficially support mammary health and growth for the cow as well as neonatal gut maturation. The most abundant miRNAs were bta-miR-125a and human homolog miR-718 based on the abundance values of read count obtained from the milk samples.bta-miR-125a is involved in host bacterial and viral immune response, and human homolog miR-718 is involved in the regulation of p53, VEGF, and IGF signaling pathways, respectively. Sixty-two miRNAs were up-regulated and 121 miRNAs were down-regulated throughout all the milk samples when compared to raw whole milk. In addition, our study explored the putative roles of other ncRNAs which included 88 piRNAs (piwi-interacting RNA), 64 antisense RNAs, and 105 lincRNAs (long-intergenic ncRNAs) contained in the bovine exosomes. CONCLUSION: Together, the results indicate that bovine milk contains significant numbers of ncRNAs with putative regulatory targets associated with immune- and developmental-functions important for neonatal bovine health, and that processing significantly affects the ncRNA expression values; but statistical testing of overall abundance(read counts) of all miRNA samples suggests abundance values aren't much affected. This can be attributed to the breakage of exosomal vesicles during the processing stages. It is worth noting, however, that these gene regulatory targets are putative, and further evidence could be generated through experimental validation.


Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , Leite/química , Animais , Bovinos , Feminino , Imunidade , MicroRNAs/genética , RNA não Traduzido/genética
11.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188642, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715268

RESUMO

Autophagy, usually referred to as macroautophagy, is a cytoprotective behavior that helps cells, especially cancer cells, escape crises. However, the role of autophagy in cancer remains controversial. The induction of autophagy is favorable for tumor growth, as it can degrade damaged cell components accumulated during nutrient deficiency, chemotherapy, or other stresses in a timely manner. Whereas the antitumor effect of autophagy might be closely related to its crosstalk with metabolism, immunomodulation, and other pathways. Recent studies have verified that lncRNAs and circRNAs modulate autophagy in carcinogenesis, cancer cells proliferation, apoptosis, metastasis, and chemoresistance via multiple mechanisms. A comprehensive understanding of the regulatory relationships between ncRNAs and autophagy in cancer might resolve chemoresistance and also offer intervention strategies for cancer therapy. This review systematically displays the regulatory effects of lncRNAs and circRNAs on autophagy in the contexts of cancer initiation, progression, and resistance to chemo- or radiotherapy and provides a novel insight into cancer therapy.


Assuntos
Autofagia/genética , Neoplasias/genética , RNA não Traduzido/metabolismo , Humanos , Neoplasias/patologia
12.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638843

RESUMO

Endometriosis is defined as endometrial-like tissue outside the uterine cavity. It is a chronic inflammatory estrogen-dependent disease causing pain and infertility in about 10% of women of reproductive age. Treatment nowadays consists of medical and surgical therapies. Medical treatments are based on painkillers and hormonal treatments. To date, none of the medical treatments have been able to cure the disease and symptoms recur as soon as the medication is stopped. The development of new biomedical targets, aiming at the cellular and molecular mechanisms responsible for endometriosis, is needed. This article summarizes the most recent medications under investigation in endometriosis treatment with an emphasis on non-coding RNAs that are emerging as key players in several human diseases, including cancer and endometriosis.


Assuntos
Sistemas de Liberação de Medicamentos , Endometriose , RNA não Traduzido/metabolismo , Animais , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Endometriose/patologia , Feminino , Humanos
14.
Molecules ; 26(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684745

RESUMO

The non-coding RNAs (ncRNA) are RNA transcripts with different sizes, structures and biological functions that do not encode functional proteins. RNA G-quadruplexes (rG4s) have been found in small and long ncRNAs. The existence of an equilibrium between rG4 and stem-loop structures in ncRNAs and its effect on biological processes remains unexplored. For example, deviation from the stem-loop leads to deregulated mature miRNA levels, demonstrating that miRNA biogenesis can be modulated by ions or small molecules. In light of this, we report several examples of rG4s in certain types of ncRNAs, and the implications of G4 stabilization using small molecules, also known as G4 ligands, in the regulation of gene expression, miRNA biogenesis, and miRNA-mRNA interactions. Until now, different G4 ligands scaffolds were synthesized for these targets. The regulatory role of the above-mentioned rG4s in ncRNAs can be used as novel therapeutic approaches for adjusting miRNA levels.


Assuntos
Quadruplex G/efeitos dos fármacos , RNA não Traduzido/química , Humanos , Sequências Repetidas Invertidas/genética , Sequências Repetidas Invertidas/fisiologia , Ligantes , MicroRNAs/genética , RNA Mensageiro/genética , RNA não Traduzido/metabolismo
15.
J Hematol Oncol ; 14(1): 141, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496946

RESUMO

Pancreatic cancer has the worst prognosis among common tumors which is attributed to its aggressive phenotype, diagnosis at advanced, inoperable stages, and resistance to systemic therapy. Non-coding RNAs (ncRNAs) such as microRNAs, long non-coding RNAs, and circular RNAs have been established as important regulators of gene expression and their deregulation has been implicated in multiple diseases and foremost cancer. In the tumor microenvironment, non-coding RNAs can be distributed among cancer cells, stromal cells, and immune cells via small extracellular vesicles (sEVs), thereby facilitating intercellular communication and influencing major cancer hallmarks such as angiogenesis, evasion of the immune system, and metastatic dissemination. Furthermore, sEV-ncRNAs have shown promising potential as liquid biopsies with diagnostic and prognostic significance. In this review, we summarize the role of sEVs as carriers of ncRNAs and underlying molecular mechanisms in pancreatic cancer. Moreover, we review the potential of sEV-ncRNAs as biomarkers and highlight the suitability of sEVs as delivery vehicles for ncRNA-based cancer therapy.


Assuntos
Vesículas Extracelulares/genética , Neoplasias Pancreáticas/genética , RNA não Traduzido/genética , Animais , Biomarcadores Tumorais/genética , Vesículas Extracelulares/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Microambiente Tumoral
16.
BMC Bioinformatics ; 22(1): 447, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544356

RESUMO

BACKGROUND: Studies have proven that the same family of non-coding RNAs (ncRNAs) have similar functions, so predicting the ncRNAs family is helpful to the research of ncRNAs functions. The existing calculation methods mainly fall into two categories: the first type is to predict ncRNAs family by learning the features of sequence or secondary structure, and the other type is to predict ncRNAs family by the alignment among homologs sequences. In the first type, some methods predict ncRNAs family by learning predicted secondary structure features. The inaccuracy of predicted secondary structure may cause the low accuracy of those methods. Different from that, ncRFP directly learning the features of ncRNA sequences to predict ncRNAs family. Although ncRFP simplifies the prediction process and improves the performance, there is room for improvement in ncRFP performance due to the incomplete features of its input data. In the secondary type, the homologous sequence alignment method can achieve the highest performance at present. However, due to the need for consensus secondary structure annotation of ncRNA sequences, and the helplessness for modeling pseudoknots, the use of the method is limited. RESULTS: In this paper, a novel method "ncDLRES", which according to learning the sequence features, is proposed to predict the family of ncRNAs based on Dynamic LSTM (Long Short-term Memory) and ResNet (Residual Neural Network). CONCLUSIONS: ncDLRES extracts the features of ncRNA sequences based on Dynamic LSTM and then classifies them by ResNet. Compared with the homologous sequence alignment method, ncDLRES reduces the data requirement and expands the application scope. By comparing with the first type of methods, the performance of ncDLRES is greatly improved.


Assuntos
Biologia Computacional , RNA não Traduzido , Redes Neurais de Computação , Conformação de Ácido Nucleico , RNA não Traduzido/genética , Alinhamento de Sequência
17.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502244

RESUMO

Premature ovarian insufficiency (POI) is defined as a loss of ovarian function before the age of 40 years, with a prevalence rate estimated at approximately 1%. It causes infertility and is related to serious long-term health consequences, including reduced life expectancy, increased cardiovascular risk, decreased bone mineral density and neurological disorders. There is currently no effective therapy for POI that is widely available in clinical practice; therefore, the treatment of patients with POI is based on hormone replacement therapy. One of the recent advances in the understanding of the pathophysiology of POI has been the role of microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) in the disease. Moreover, intensive research on human folliculogenesis and reproductive biology has led to the development of novel promising therapeutic strategies with the use of exosomal miRNAs derived from mesenchymal stem cells to restore ovarian function in POI patients. This narrative review focuses on the new studies concerning the role of ncRNAs in the pathogenesis of POI, together with their potential as biomarkers of the disease and targets for therapy.


Assuntos
Terapia de Alvo Molecular , Insuficiência Ovariana Primária/fisiopatologia , Insuficiência Ovariana Primária/terapia , RNA não Traduzido/genética , Feminino , Humanos , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia
18.
Elife ; 102021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477109

RESUMO

Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from cochlear supporting cells (SCs) have been unsuccessful, notably lacking expression of the key OHC motor protein, Prestin. Thus, regeneration of Prestin+ OHCs represents a barrier to restore auditory function in vivo. Here, we reported the successful in vivo conversion of adult mouse cochlear SCs into Prestin+ OHC-like cells through the concurrent induction of two key transcriptional factors known to be necessary for OHC development: Atoh1 and Ikzf2. Single-cell RNA sequencing revealed the upregulation of 729 OHC genes and downregulation of 331 SC genes in OHC-like cells. The resulting differentiation status of these OHC-like cells was much more advanced than previously achieved. This study thus established an efficient approach to induce the regeneration of Prestin+ OHCs, paving the way for in vivo cochlear repair via SC transdifferentiation.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cóclea/citologia , Células Ciliadas Auditivas/fisiologia , Fator de Transcrição Ikaros/metabolismo , RNA não Traduzido/metabolismo , Transportadores de Sulfato/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas , Diferenciação Celular , Biologia Computacional , Antagonistas de Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Técnicas de Introdução de Genes , Fator de Transcrição Ikaros/genética , Camundongos , Microscopia Eletrônica de Varredura , Proteínas Motores Moleculares/genética , Proteínas Motores Moleculares/metabolismo , RNA/genética , RNA/metabolismo , RNA não Traduzido/genética , Análise de Sequência de RNA , Análise de Célula Única , Transportadores de Sulfato/genética , Tamoxifeno/farmacologia
19.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502386

RESUMO

Understanding the pathophysiology of rheumatoid arthritis (RA) has led to the successful development of molecule-targeted drugs for the treatment of RA. However, some RA patients are refractory to these treatments, suggesting that the pathological mechanism of the disease is not entirely understood. Genome and transcriptome analysis is essential for understanding the unknown pathophysiology of human diseases. Rapid and more comprehensive gene analysis technologies have revealed notable changes in the expression of coding RNA and non-coding RNA in RA patients. This review focuses on the current state of non-coding RNA research in relation to RA, especially on tRNA fragments. Interestingly, it has been found that tRNA fragments repress translation and are antiapoptotic. The association between tRNA fragments and various diseases has been studied, and this article reviews the possible role of tRNA fragments in RA.


Assuntos
Artrite Reumatoide/genética , RNA de Transferência/genética , RNA não Traduzido/genética , Artrite Reumatoide/fisiopatologia , Grânulos Citoplasmáticos/genética , Grânulos Citoplasmáticos/metabolismo , Humanos , Biossíntese de Proteínas/genética , RNA/genética , RNA de Transferência/metabolismo , RNA não Traduzido/metabolismo , Silício , Estresse Fisiológico/genética , Titânio
20.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502399

RESUMO

B-lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies are of B-cell origin, suggesting that the development and activation of B cells must be tightly regulated. In recent years, differentially expressed non-coding RNAs have been identified in mantle cell lymphoma (MCL) tumor samples as opposed to their naive, normal B-cell compartment. These aberrantly expressed molecules, specifically microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), have a role in cellular growth and survival pathways in various biological models. Here, we provide an overview of current knowledge on the role of non-coding RNAs and their relevant targets in B-cell development, activation and malignant transformation, summarizing the current understanding of the role of aberrant expression of non-coding RNAs in MCL pathobiology with perspectives for clinical use.


Assuntos
Linfócitos B/metabolismo , Linfoma de Célula do Manto/genética , RNA não Traduzido/genética , Linfócitos B/fisiologia , Biomarcadores/metabolismo , Ciclo Celular/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/metabolismo , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfoma de Célula do Manto/metabolismo , MicroRNAs/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA não Traduzido/metabolismo , Transcriptoma/genética
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