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1.
Nat Commun ; 11(1): 4980, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020477

RESUMO

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.


Assuntos
Neoplasias/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Carcinogênese , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Sumoilação , Proteína Supressora de Tumor p53/genética , Ubiquitinação
2.
Nat Commun ; 11(1): 4755, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958772

RESUMO

We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.


Assuntos
Homeostase , Oxigênio/metabolismo , RNA Longo não Codificante/fisiologia , Esteróis/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Colesterol/metabolismo , Estrogênios/metabolismo , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Humanos , Células MCF-7 , Fenótipo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
3.
Sheng Wu Gong Cheng Xue Bao ; 36(8): 1504-1514, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32924349

RESUMO

MicroRNA (miRNA) is a type of highly conserved nucleotide sequence composed of 18 to 25 nucleotides, which can specifically bind to the 3'-noncoding regions of mRNA, and then play a negative regulatory role in degrading mRNA or inhibiting translation. Long non-coding RNA (lncRNA) is a type of nucleotide sequence that exceeds 200 nucleotides in length and cannot encode proteins or can only encode protein peptides. It regulates gene expression at the levels of epigenetic, transcriptional and post-transcriptional. As an important energy storage organ, fat plays an important role in regulating the energy balance of animals, and is closely related to meat production traits such as meat production and meat quality. And the disorder of fat function can lead to hyperlipidemia, type 2 diabetes and a series of cardiovascular diseases, so the molecular regulation mechanism of animal fat deposition has attracted more attention. In recent years, more and more studies have found that miRNA and lncRNA play a crucial role in animal fat deposition. We review here the current research progresses in the role of miRNA and lncRNA in animal fat deposition, to provide theoretical guidance and new ideas for further revealing the molecular regulation mechanism of animal fat deposition.


Assuntos
Tecido Adiposo , MicroRNAs , RNA Longo não Codificante , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus Tipo 2 , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro
4.
Ecotoxicol Environ Saf ; 205: 111327, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961493

RESUMO

Exposure to PM2.5 can cause serious harm to the respiratory system. Until now, although many toxicological studies have shown that pulmonary fibrosis can be caused by long-term PM2.5 exposure, there is no evidence that Endothelial-Mesenchymal Transition (EndMT) can trigger the process of pulmonary fibrosis after exposure. LncRNAs are a class of non-coding RNAs detected in mammalian cells. Nevertheless, researchers have not found whether lncRNAs participate in PM2.5 induced EndMT during pathophysiological duration. The Balb/c mouse model was exposed to PM2.5 for 4 months by dynamic intoxication. The levels of specific endothelial and mesenchymal markers were evaluated by molecular biology experiments to elucidate the mechanisms of EndMT induced by PM2.5 in lung tissues. LncRNA microarray analysis of the established mouse model of PM2.5 exposure was performed. Based on a bioinformatics analysis and RT-qPCR analysis, lncRNA Gm16410 attracted our attention. The change of lncRNA Gm16410 in mouse pulmonary vascular endothelial cells (MHCs) exposed to PM2.5 was verified, and the mechanism of lncRNA Gm16410 in EndMT was discussed. The changes of cell function were evaluated by cell migration and proliferation experiments. The molecular biology experiments proved that PM2.5 induced EndMT by activating the TGF-ß1/Smad3/p-Smad3 pathway in vitro. The relationship of EndMT and lncRNA Gm16410 was verified in mouse lung tissues and MHC cells by PM2.5 exposure. The involvement of lncRNA Gm16410 in PM2.5-induced EndMT highlights the potential of lncRNA to promote pulmonary fibrosis under environmental pollution.


Assuntos
Material Particulado/toxicidade , RNA Longo não Codificante/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Camundongos , Material Particulado/metabolismo , Fibrose Pulmonar/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3 , Fator de Crescimento Transformador beta1/metabolismo
5.
BMC Bioinformatics ; 21(1): 377, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883200

RESUMO

BACKGROUND: A large number of experimental studies show that the mutation and regulation of long non-coding RNAs (lncRNAs) are associated with various human diseases. Accurate prediction of lncRNA-disease associations can provide a new perspective for the diagnosis and treatment of diseases. The main function of many lncRNAs is still unclear and using traditional experiments to detect lncRNA-disease associations is time-consuming. RESULTS: In this paper, we develop a novel and effective method for the prediction of lncRNA-disease associations using network feature similarity and gradient boosting (LDNFSGB). In LDNFSGB, we first construct a comprehensive feature vector to effectively extract the global and local information of lncRNAs and diseases through considering the disease semantic similarity (DISSS), the lncRNA function similarity (LNCFS), the lncRNA Gaussian interaction profile kernel similarity (LNCGS), the disease Gaussian interaction profile kernel similarity (DISGS), and the lncRNA-disease interaction (LNCDIS). Particularly, two methods are used to calculate the DISSS (LNCFS) for considering the local and global information of disease semantics (lncRNA functions) respectively. An autoencoder is then used to reduce the dimensionality of the feature vector to obtain the optimal feature parameter from the original feature set. Furthermore, we employ the gradient boosting algorithm to obtain the lncRNA-disease association prediction. CONCLUSIONS: In this study, hold-out, leave-one-out cross-validation, and ten-fold cross-validation methods are implemented on three publicly available datasets to evaluate the performance of LDNFSGB. Extensive experiments show that LDNFSGB dramatically outperforms other state-of-the-art methods. The case studies on six diseases, including cancers and non-cancers, further demonstrate the effectiveness of our method in real-world applications.


Assuntos
Algoritmos , Neoplasias/patologia , RNA Longo não Codificante/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Área Sob a Curva , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Neoplasias/genética , RNA Longo não Codificante/genética , Curva ROC
6.
Nat Commun ; 11(1): 4551, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917870

RESUMO

Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.


Assuntos
Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética , Idoso , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oncogenes/genética , Estudos Prospectivos , RNA Circular/genética , RNA Longo não Codificante/genética , Análise Espacial
7.
Rev Assoc Med Bras (1992) ; 66(7): 898-903, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32844929

RESUMO

OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neuroblastoma , RNA Longo não Codificante , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Prognóstico , RNA Longo não Codificante/metabolismo
8.
Vascul Pharmacol ; 133-134: 106778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32784009

RESUMO

Angiogenesis has critical roles in numerous physiologic processes during embryonic and adult life such as wound healing and tissue regeneration. However, aberrant angiogenic processes have also been involved in the pathogenesis of several disorders such as cancer and diabetes mellitus. Vascular endothelial growth factor (VEGF) is implicated in the regulation of this process in several physiologic and pathologic conditions. Notably, several non-coding RNAs (ncRNAs) have been shown to influence angiogenesis through modulation of expression of VEGF or other angiogenic factors. In the current review, we summarize the function and characteristics of microRNAs and long non-coding RNAs which regulate angiogenic processes. Understanding the role of these transcripts in the angiogenesis can facilitate design of therapeutic strategies to defeat the pathogenic events during this process especially in the human malignancies. Besides, angiogenesis-related mechanisms can improve tissue regeneration after conditions such as arteriosclerosis, myocardial infarction and limb ischemia. Thus, ncRNA-regulated angiogenesis can be involved in the pathogenesis of several disorders.


Assuntos
Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neovascularização Patológica , Neovascularização Fisiológica , RNA Longo não Codificante/metabolismo , Animais , Células Endoteliais/patologia , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Fisiológica/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Microambiente Tumoral
9.
DNA Cell Biol ; 39(9): 1558-1572, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32845706

RESUMO

Sarcomas are a broad family of cancers that arise from cells of mesenchymal origin in virtually every tissue of the body. Some transcription factors (TFs) have been reported to be involved in the pathogenesis and metastasis of sarcomas. The expression of certain long noncoding RNAs (lncRNAs) has been correlated with the degree of cancer prognosis. There is an urgent need to effectively integrate TFs and lncRNA/microRNA/mRNA regulatory axis and further identify more key regulators that play crucial roles in sarcomas. We performed a network-based computational analysis to investigate the lncRNA-TF cross talks via integrating lncRNA-TF ceRNA interactions and TF-TF protein-protein interactions. Multiple topology analyses were performed to the sarcomas-related global lncRNA-TF network. Several lncRNAs or TFs with central topology structures were identified as key regulators and used to locate a hub-associated lncRNA-TF subnetwork. Three functional modules were identified from the sarcomas-related global lncRNA-TF network, which have shown significant pathway enrichment and prognosis capability. The lncRNAs and TFs of these modules were shown to participate in sarcoma-related biological phenomena through involving in mitogen-activated protein kinases (MAPK), Jak-STAT, and transforming growth factor (TGF-beta) signaling pathways. More importantly, a subset of core lncRNA-TF cross talks that might form positive feedback loops to control biological processes of sarcomas was identified. These core lncRNA-TF positive feedback loops showed more TF binding affinity than other lncRNAs. All the results can help us uncover the molecular mechanism of sarcomas and provide a novel way for diagnosis biomarker and therapeutic target identification.


Assuntos
Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Sarcoma/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Retroalimentação Fisiológica , Humanos , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante/metabolismo , Sarcoma/patologia , Fatores de Transcrição/metabolismo
10.
BMC Bioinformatics ; 21(1): 372, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854616

RESUMO

BACKGROUND: About 90% of patients who have diabetes suffer from Type 2 DM (T2DM). Many studies suggest using the significant role of lncRNAs to improve the diagnosis of T2DM. Machine learning and Data Mining techniques are tools that can improve the analysis and interpretation or extraction of knowledge from the data. These techniques may enhance the prognosis and diagnosis associated with reducing diseases such as T2DM. We applied four classification models, including K-nearest neighbor (KNN), support vector machine (SVM), logistic regression, and artificial neural networks (ANN) for diagnosing T2DM, and we compared the diagnostic power of these algorithms with each other. We performed the algorithms on six LncRNA variables (LINC00523, LINC00995, HCG27_201, TPT1-AS1, LY86-AS1, DKFZP) and demographic data. RESULTS: To select the best performance, we considered the AUC, sensitivity, specificity, plotted the ROC curve, and showed the average curve and range. The mean AUC for the KNN algorithm was 91% with 0.09 standard deviation (SD); the mean sensitivity and specificity were 96 and 85%, respectively. After applying the SVM algorithm, the mean AUC obtained 95% after stratified 10-fold cross-validation, and the SD obtained 0.05. The mean sensitivity and specificity were 95 and 86%, respectively. The mean AUC for ANN and the SD were 93% and 0.03, also the mean sensitivity and specificity were 78 and 85%. At last, for the logistic regression algorithm, our results showed 95% of mean AUC, and the SD of 0.05, the mean sensitivity and specificity were 92 and 85%, respectively. According to the ROCs, the Logistic Regression and SVM had a better area under the curve compared to the others. CONCLUSION: We aimed to find the best data mining approach for the prediction of T2DM using six lncRNA expression. According to the finding, the maximum AUC dedicated to SVM and logistic regression, among others, KNN and ANN also had the high mean AUC and small standard deviations of AUC scores among the approaches, KNN had the highest mean sensitivity and the highest specificity belonged to SVM. This study's result could improve our knowledge about the early detection and diagnosis of T2DM using the lncRNAs as biomarkers.


Assuntos
Algoritmos , Diabetes Mellitus Tipo 2/diagnóstico , RNA Longo não Codificante/metabolismo , Área Sob a Curva , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/genética , Diagnóstico Precoce , Humanos , Modelos Logísticos , Curva ROC , Sensibilidade e Especificidade , Máquina de Vetores de Suporte
11.
Gene ; 762: 145016, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777522

RESUMO

Mcl-1 is a member of the Bcl-2 anti-apoptotic protein family with important roles in the development, lifespan and metabolism of lymphocytes, as well as oncogenesis. Mcl-1 displays the shortest half-life of all Bcl-2 family members, with miRNA interference and proteasomal degradation being major pathways for Mcl-1 downregulation. In this study, we have identified a previously undescribed control mechanism active at the RNA level. A divergently transcribed lncRNA LOC107985203 (named here mcl1-AS1) negatively modulated Mcl-1 expression resulting in downregulation of Mcl-1 at both mRNA and protein level in a time-dependent manner. Using reporter assays, we confirmed that the mcl1-AS1 lncRNA promoter was located within Mcl-1 coding region. We next placed mcl1-AS1 under tetracycline-inducible control and demonstrated decreased viability in HEK293 cells upon doxycycline induction. Inhibition of mcl1-AS1 with shRNA reversed drug sensitivity. Bioinformatics surveys predicted direct mcl1-AS1 lncRNA binding to Mcl-1 transcripts, suggesting its mechanism in Mcl-1 expression is at the transcriptional level, consistent with a common role for anti-sense transcripts. The identification of a bi-directional promoter and lncRNA controlling Mcl-1 expression will have implications for controlling Mcl-1 activity in cancer cells, or for the purpose of enhancing the lifespan and quality of anti-cancer T lymphocytes.


Assuntos
Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Éxons , Células HEK293 , Humanos , Íntrons , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Regiões Promotoras Genéticas , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
PLoS Genet ; 16(8): e1008930, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760061

RESUMO

Genomic imprinting is a parent-of-origin dependent phenomenon that restricts transcription to predominantly one parental allele. Since the discovery of the first long noncoding RNA (lncRNA), which notably was an imprinted lncRNA, a body of knowledge has demonstrated pivotal roles for imprinted lncRNAs in regulating parental-specific expression of neighboring imprinted genes. In this Review, we will discuss the multiple functionalities attributed to lncRNAs and how they regulate imprinted gene expression. We also raise unresolved questions about imprinted lncRNA function, which may lead to new avenues of investigation. This Review is dedicated to the memory of Denise Barlow, a giant in the field of genomic imprinting and functional lncRNAs. With her passion for understanding the inner workings of science, her indominable spirit and her consummate curiosity, Denise blazed a path of scientific investigation that made many seminal contributions to genomic imprinting and the wider field of epigenetic regulation, in addition to inspiring future generations of scientists.


Assuntos
Impressão Genômica , RNA Longo não Codificante/genética , Animais , Humanos , RNA Longo não Codificante/metabolismo
13.
J Environ Pathol Toxicol Oncol ; 39(2): 101-111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749120

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to be involved in cancer initiation and evolution, including colorectal cancer (CRC). Nuclear-enriched abundant transcript 1 (NEAT1) exerts important functions in multiple cancers; however, the specific modulatory mechanism in CRC demands in-depth exploration. The expression levels of NEAT1, microRNA-195-5p (miR-195-5p), and centrosomal protein 55 (CEP55) were examined using quantitative real-time polymerase chain reaction (qRT-PCR), and protein expression of CEP55 was detected by Western blot assay. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazole-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastasis ability. Dual-luciferase reporter assay was used to analyze the correlation among NEAT1, miR-195-5p and CEP55. The expression of NEAT1 was up-regulated in CRC tissues and cells, and overall survival was lower with high expression of NEAT1. Knockdown of NEAT1 repressed cell proliferation, migration, and invasion, while inducing apoptosis in CRC cells. NEAT1 targeted miR-195-5p and inhibited the expression of miR-195-5p. Silence of NEAT1 inhibited CRC cell proliferation, migration, and invasion, and promoted apoptosis by up-regulating miR-195-5p. MiR-195-5p targeted and suppressed CEP55 expression, and CEP55 reverted the effects induced by miR-195-5p. NEAT1 regulated the expression of CEP55 through miR-195-5p. NEAT1 promotes colorectal cancer cellular processes by regulating CEP55 expression via the sponging of miR-195-5p. Therefore, NEAT1 might play a crucial role in CRC treatments.


Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Mucosa Gástrica/citologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo
14.
Wiley Interdiscip Rev RNA ; 11(5): e1614, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32638509

RESUMO

Coronaviruses, including SARS-Cov-2, are RNA-based pathogens that interface with a large variety of RNA-related cellular processes during infection. These processes include capping, polyadenylation, localization, RNA stability, translation, and regulation by RNA binding proteins or noncoding RNA effectors. The goal of this article is to provide an in-depth perspective on the current state of knowledge of how various coronaviruses interact with, usurp, and/or avoid aspects of these cellular RNA biology machineries. A thorough understanding of how coronaviruses interact with RNA-related posttranscriptional processes in the cell should allow for new insights into aspects of viral pathogenesis as well as identify new potential avenues for the development of anti-coronaviral therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease.


Assuntos
Betacoronavirus/genética , Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Viral/genética , Animais , Betacoronavirus/metabolismo , Humanos , MicroRNAs/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido , Poliadenilação , Biossíntese de Proteínas , Edição de RNA , Processamento de RNA , Estabilidade de RNA , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Vírus da SARS/genética , Vírus da SARS/metabolismo
15.
Int J Exp Pathol ; 101(3-4): 96-105, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32608553

RESUMO

Long non-coding RNAs (lncRNAs) have been proven to play important roles in various cancers, including gastric cancer (GC). However, detailed knowledge about lncRNAs in GC is limited. Therefore we carried out an in-depth study of public data and found 83 differently expressed lncRNAs in GC. To further confirm the target genes of these lncRNAs, we constructed a co-expression network between lncRNAs and mRNAs and found three lncRNAs (MBNL1-AS1, HAND2-AS1 and MIR100HG) were at the core of the network. By coalition analysis of clinical information and the three lncRNAs' expression level from The Cancer Genome Atlas (TCGA) and GSE15459 data sets, we found MIR100HG could be a potential prognostic factor. Clinical samples showed patients with higher MIR100HG expression had poorer prognosis, and further experiments demonstrated that MIR100HG was associated with proliferation, migration and invasion of GC cells. Hopefully, MIR100HG might be considered as a novel prognostic factor and biomarker for GC.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
16.
Life Sci ; 257: 118035, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622950

RESUMO

Despite the recent scientific advances made in cancer diagnostics and therapeutics, cancer still remains the second leading cause of death worldwide. Thus, there is a need to identify new potential biomarkers/molecular targets to improve the diagnosis and treatment of cancer patients. In this regard, long non-coding RNAs (lncRNAs), a type of non-coding RNA molecule, have been found to play important roles in diverse biological processes, including tumorigenesis, and may provide new biomarkers and/or molecular targets for the improved detection of treatment of cancer. For example, one lncRNA, tissue differentiation-inducing non-protein coding RNA (TINCR) has been found to be significantly dysregulated in many cancers, and has an impact on tumor development and progression through targeting pivotal molecules in cancer-associated signaling pathways. Hence, based on recent discoveries, herein, we discuss the regulatory functions and the underlying mechanisms of how TINCR regulates signaling pathways attributed to cancer hallmarks associated with the pathogenesis of various human cancers. We also highlight studies assessing its potential clinical utility as a biomarker/target for early detection, cancer risk stratification, and personalized cancer therapies.


Assuntos
Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias/metabolismo , Transdução de Sinais/genética
17.
Life Sci ; 257: 118013, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603818

RESUMO

AIMS: Emerging literature illustrates critical roles of long noncoding RNAs (lncRNAs) in the progression of atherosclerosis. However, the biological functions and mechanism by which lncRNAs regulate the atherosclerosis remain unclear. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidative low-density lipoprotein (ox-LDL). RNA and protein levels were respectively measured using RT-qPCR and western blot. Molecular interaction was detected using luciferase reporter assay and chromatin immunoprecipitation (ChIP). Proliferation and migration were measured using CCK-8 and wound healing assay. KEY FINDINGS: Here, results unveiled that lncRNA SNHG7 was remarkedly up-regulated in ox-LDL exposed HUVECs. Gain and loss of function experiments showed that the SNHG7 repressed the proliferation and migration of HUVECs. Mechanistically, transcription factor E2F1 was found to target the promoter region of lncRNA SNHG7 and accelerated its expression. Moreover, miR-186-5p was found to bind with the 3'-UTR of SNHG7, meanwhile miR-186-5p also bound with the MMP2 mRNA 3'-UTR. SIGNIFICANCE: In conclusion, these results show the essential roles of E2F1/SNHG7/miR-186-5p/MMP2 axis on the proliferation and migration of endothelial cells, providing a potential therapeutic target for atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Células Endoteliais/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Aterosclerose/fisiopatologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fator de Transcrição E2F1/metabolismo , Células Endoteliais/fisiologia , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia
18.
Mol Cell ; 79(3): 443-458.e7, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32649883

RESUMO

Despite the prominent role of TDP-43 in neurodegeneration, its physiological and pathological functions are not fully understood. Here, we report an unexpected role of TDP-43 in the formation of dynamic, reversible, liquid droplet-like nuclear bodies (NBs) in response to stress. Formation of NBs alleviates TDP-43-mediated cytotoxicity in mammalian cells and fly neurons. Super-resolution microscopy reveals distinct functions of the two RRMs in TDP-43 NB formation. TDP-43 NBs are partially colocalized with nuclear paraspeckles, whose scaffolding lncRNA NEAT1 is dramatically upregulated in stressed neurons. Moreover, increase of NEAT1 promotes TDP-43 liquid-liquid phase separation (LLPS) in vitro. Finally, we discover that the ALS-associated mutation D169G impairs the NEAT1-mediated TDP-43 LLPS and NB assembly, causing excessive cytoplasmic translocation of TDP-43 to form stress granules, which become phosphorylated TDP-43 cytoplasmic foci upon prolonged stress. Together, our findings suggest a stress-mitigating role and mechanism of TDP-43 NBs, whose dysfunction may be involved in ALS pathogenesis.


Assuntos
Esclerose Amiotrófica Lateral/genética , Proteínas de Ligação a DNA/genética , Corpos de Inclusão Intranuclear/metabolismo , Neurônios/metabolismo , RNA Longo não Codificante/genética , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Animais , Animais Geneticamente Modificados , Arsenitos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Drosophila melanogaster , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Corpos de Inclusão Intranuclear/efeitos dos fármacos , Corpos de Inclusão Intranuclear/ultraestrutura , Camundongos , Mutação , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Cultura Primária de Células , Transporte Proteico/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Estresse Fisiológico
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(1): 113-117, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32621415

RESUMO

Atherosclerosis is an important pathological basis for coronary artery disease. ANRIL is an antisense non-coding RNA located in Chr9p21 locus, which was identified as the most significant risk locus associated with atherosclerosis. ANRIL can produce multiple transcripts including linear and circular transcripts after various transcript splicing. It has been illustrated that ANRIL plays important roles in the pathology of atherosclerosis by regulating the proliferation and apoptosis of vascular cells. Linear ANRIL can regulate the proliferation of vascular smooth muscle cells (VSMCs) in plaques by chromatin modification, as well as influence the proliferation and the apoptosis of macrophages in post transcription; circular ANRIL can affect the proliferation and apoptosis of VSMCs by chromatin modification as well as interfering with rRNA maturation. In this review, we describe the ANRIL evolution, different transcripts characteristics, and their roles in the proliferation and apoptosis of vascular cells to participate in the process of atherosclerosis, for further understanding the pathogenesis of atherosclerosis and finding potential targets for diagnosis and treatment of atherosclerosis.


Assuntos
Aterosclerose , RNA Longo não Codificante , Apoptose/genética , Aterosclerose/genética , Proliferação de Células/genética , Humanos , Miócitos de Músculo Liso/patologia , RNA Longo não Codificante/metabolismo
20.
DNA Cell Biol ; 39(9): 1532-1544, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32644844

RESUMO

Increasing evidence suggests that aberrant long noncoding (lnc) RNA expression plays a vital role in gastric cancer (GC) initiation and progression. Thus, we aimed to develop a lncRNA-based risk signature and nomogram to predict overall survival (OS) for patients with GC. Our primary cohort was composed of 341 patients with clinical and lncRNA expression data in The Cancer Genome Atlas stomach adenocarcinoma (TCGA STAD), the internal validation cohort was composed of 172 randomly assigned patients, and the external validation cohort was composed of 300 patients from GSE62254 dataset. A risk signature and nomogram were developed for the primary cohort and validated on the validation cohorts. Furthermore, gene set enrichment analysis (GSEA) was used to investigate the pathway enrichment for the risk signature. The expression patterns of several lncRNAs were also investigated in clinical samples from 10 GC patients. We identified and validated a 14-lncRNA signature highly associated with the OS of patients with GC, which performed well on evaluation with C-index, area under the curve, and calibration curves. In addition, univariate and multivariate Cox regression analyses indicated that the lncRNA signature was an independent predictive factor for GC patients. Therefore, a nomogram incorporating lncRNA signature and clinical factors was constructed to predict OS for patients with GC in primary cohort that suggested powerful predictive values for survival in the TCGA cohort and the other two validation cohorts. In addition, GSEA indicated that the identified lncRNAs may regulate the autophagy pathway, affecting tumorigenesis and prognosis of patients with GC. Experimental validation demonstrated that the expression of lncRNAs showed the same trend both in our clinical samples and STAD dataset. These results suggest that both risk signature and nomogram were effective prognostic indicators for patients with GC.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Autofagia/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia , Análise de Sobrevida , Transcriptoma
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