Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 464
Filtrar
1.
Gene ; 766: 145113, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32891771

RESUMO

Breast cancer remains the most common malignancy in women worldwide. Circular RNAs (circRNAs) are a newly validated type of endogenous non-coding RNAs and accumulating evidence suggests that aberrant circRNAs are involved in disease pathogenesis. However, the function of circRNAs in breast cancer remains largely unknown. This study is aimed to characterize the potential role and mechanism of hsa_circ_0000442 (circ_0000442) in breast cancer. The human breast epithelial cell line (MCF-10A), breast cancer cell lines (MCF-7, T47D, BT474, SK-BR-3, MDA-MB-231, SUM-1315) and the Balb/C Nude mice were used for exploration, and the qRT-PCR, western blot, dual-luciferase reporter assay, glo assay, colony formation assay, and tumor xenograft were carried out for investigation. In this study, the results showed a lower expression of circ_0000442 in breast cancer tumor tissues compared with the adjacent normal tissues. Subsequently, circ_0000442 was found to acted as the sponge of miR-148b-3p in breast cancer cells, thus exerting the tumor-suppressive effects. In the subsequent mechanism study, results showed that miR-148b-3p directly targeted PTEN, a well-known tumor suppressor which negatively regulats PI3K/Akt pathway, thus promoting tumor growth in breast cancer. Overall, this study for the first time identified the tumor-suppressive role of circ_0000442 in breast cancer and found PTEN as a novel direct target of miR-148b-3p. The regulatory role of circ_0000442/miR-148b-3p/PTEN/PI3K/Akt axis was preliminarily confirmed in breast cancer cells and mouse models. These findings suggest an important progress in our standing of breast cancer and lay the foundation for the further function, diagnosis, therapy and prognosis research of circular RNAs in breast cancer.


Assuntos
Neoplasias da Mama/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Circular/genética , Transdução de Sinais/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Prognóstico
2.
Gene ; 766: 145154, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32949699

RESUMO

CircRNA serves a crucial role in the development of heart failure (HF). Nevertheless, the regulatory mechanisms of circ_0062389 in HF are unknown. This study aims to examine the effect and mechanism of circ_0062389 on cardiomyocyte apoptosis in HF rats and H9C2 cells. Rats were divided into 5 groups (n = 8/group): the Control group, Sham group, HF group, HF + si-NC group, and HF + si-circRNA group. The echocardiography was used to examine the cardiac function, including LVIDd, LVIDs, IVSd, and IVSs. The apoptosis of myocardial tissue was detected through TUNEL method. H9C2 cells were randomly assigned into Control group (untransfected H9C2 cells), H/R group (untransfected H/R H9C2 cells), H/R + si-NC group (transfected si-NC) and H/R + si-circRNA group (transfect si-circ_0062389). Cell apoptosis was assessed through flow cytometry. The expression of circ_0062389 in myocardial tissues of HF rats was significantly higher than that of Control group and Sham group. Silencing circ_0062389 significantly reduced the levels of LVIDd, LVIDs, IVSd, and IVSs. Additionally, silencing circ_0062389 could significantly reduce the apoptosis rate of rat cardiomyocytes. Besides, silencing circ_0062389 significantly reduced the expression of TGF-ß1 and Smad3 protein. Silencing circ_0062389 could alleviate cardiomyocyte apoptosis in HF rats via modulating TGF-ß1/Smad3 signaling pathway, which might be a promising target for the treatment of HF.


Assuntos
Apoptose/genética , Insuficiência Cardíaca/genética , Miócitos Cardíacos/patologia , Interferência de RNA/fisiologia , RNA Circular/genética , Transdução de Sinais/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Animais , Linhagem Celular , Coração/fisiologia , Insuficiência Cardíaca/patologia , Masculino , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
3.
Nat Commun ; 11(1): 5611, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154349

RESUMO

Fine-tuning of insulin release from pancreatic ß-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of ß-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding ß-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.


Assuntos
Secreção de Insulina/genética , Insulina/genética , Íntrons , RNA Circular/metabolismo , Animais , Sinalização do Cálcio , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Camundongos , RNA Circular/genética , Ratos
5.
Nucleic Acids Res ; 48(18): 10368-10382, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32955563

RESUMO

Circular RNAs (circRNAs) encompass a widespread and conserved class of RNAs, which are generated by back-splicing of downstream 5' to upstream 3' splice sites. CircRNAs are tissue-specific and have been implicated in diseases including cancer. They can function as sponges for microRNAs (miRNAs) or RNA binding proteins (RBPs), for example. Moreover, some contain open reading frames (ORFs) and might be translated. The functional relevance of such peptides, however, remains largely elusive. Here, we report that the ORF of circZNF609 is efficiently translated when expressed from a circZNF609 overexpression construct. However, endogenous proteins could not be detected. Moreover, initiation of circZNF609 translation is independent of m6A-generating enzyme METTL3 or RNA sequence elements such as internal ribosome entry sites (IRESs). Surprisingly, a comprehensive mutational analysis revealed that deletion constructs, which are deficient in producing circZNF609, still generate the observed protein products. This suggests that the apparent circZNF609 translation originates from trans-splicing by-products of the overexpression plasmids and underline that circRNA overexpression constructs need to be evaluated carefully, particularly when functional studies are performed.


Assuntos
Sítios Internos de Entrada Ribossomal/genética , Metiltransferases/genética , Biossíntese de Proteínas , RNA Circular/genética , Sequência de Bases/genética , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , MicroRNAs/genética , Sítios de Splice de RNA/genética , RNA Circular/classificação , Proteínas de Ligação a RNA/genética
6.
DNA Cell Biol ; 39(11): 2059-2076, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960090

RESUMO

The liver has an excellent capacity for regeneration when faced with external injury and the damage differs from that of other organs in the body. Our aim was to identify the role of circular RNA (circRNA) during the DNA synthesis phase (36 h) of mice liver regeneration. High-throughput RNA sequencing was conducted to explore circRNA and messenger RNA (mRNA) expression in three pairs of mice liver tissue at 0 and 36 h after 2/3 partial hepatectomy. One hundred differentially expressed circRNAs were detected, including 66 upregulated and 34 downregulated circRNAs. We also explored 2483 differentially expressed mRNAs, including 1422 upregulated and 1061 downregulated mRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes indicated that cell cycle regulation, material metabolism, and multiple classical pathways were involved in the DNA synthesis process. A competing endogenous RNA (ceRNA) network containing 5 circRNAs, 28 target genes, and 533 microRNAs (miRNAs) was constructed, and we selected the top 5 miRNAs to map it. Potential key circRNAs were validated with the quantitative real-time PCR technique and their regeneration curves, including consecutive time points, were produced. Finally, a cell counting kit-8 assay on key circRNAs of ceRNA network was performed to further confirm their roles in the DNA synthesis phase of liver regeneration. This study provides a circRNA expression profile for liver regeneration and contributes valuable information for future research.


Assuntos
DNA/biossíntese , Regeneração Hepática/genética , RNA Circular/genética , RNA-Seq , Animais , DNA/genética , Replicação do DNA/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Ontologia Genética , Humanos , Camundongos , MicroRNAs/genética
7.
DNA Cell Biol ; 39(11): 1938-1947, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32991198

RESUMO

Circular RNAs (circRNAs), a novel group of noncoding RNAs, are present in most eukaryotic cells. Different from messenger RNAs, circRNAs have a covalently closed single-stranded stable structure and often act in cell type and tissue-specific manners, indicating that they can be used as biomarkers. With the advance of high-throughput RNA sequencing technology and bioinformatics, a large number of circRNAs have been identified in association with musculoskeletal diseases, but the functions of most circRNAs have not been clarified. circRNAs regulate biological processes by adsorbing microRNA as "sponges," binding to proteins, acting as transcriptional regulators, and participating in translation of proteins. In this study, we discuss the latest understanding of biogenesis and gene regulatory mechanisms of circRNAs with special emphasis on new targets for musculoskeletal disease diagnosis and clinical treatment.


Assuntos
Biomarcadores/sangue , Doenças Musculoesqueléticas/sangue , RNA Circular/sangue , Biomarcadores/metabolismo , Biologia Computacional , Regulação da Expressão Gênica/genética , Humanos , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/patologia , RNA Circular/genética , RNA Mensageiro/genética , RNA não Traduzido/sangue , RNA não Traduzido/genética
8.
Arch Insect Biochem Physiol ; 105(3): e21735, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32881053

RESUMO

The disease caused by Bombyx mori nucleopolyhedrovirus (BmNPV) has always been difficult to control, resulting in tremendous economic losses in the sericulture industry. Although much has been learned about the impact of noncoding RNAs on pathogenesis, the role of circular RNA (circRNA) in insect immunity remains unclear. To explore circRNA regulation involved in BmNPV infection, we used transcriptome analysis of BmN cells with or without BmNPV infection to generate circRNA data set. A total of 444 novel circRNAs were identified in BmN cells, with 198 pervasively distributed both in the control group and BmNPV-infection group. The host genes were enriched inMAPK signaling pathway, dorso-ventral axis formation, and ECM-receptor interaction, which were required for the normal larval growth. A total of 75 circRNAs were differentially expressed (DE) on BmNPV infection. Six downregulated circRNAs were validated by Sanger sequencing and qRT-PCR. DEcircRNA-miRNA-DEmRNA network was constructed based on the six validated circRNAs. Pathway analysis indicated that the predicted target genes were mainly enriched in the metabolic pathway and immune-related signaling pathway. Our results may provide a basis for further studies on circRNA function in BmN cells challenged by BmNPV infection and offer an insight into the molecular mechanism on silkworm-virus interaction.


Assuntos
Bombyx/genética , Bombyx/virologia , Nucleopoliedrovírus/fisiologia , RNA Circular/genética , Animais , Bombyx/imunologia , Linhagem Celular , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Transdução de Sinais
9.
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
10.
PLoS One ; 15(8): e0231125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866172

RESUMO

Korean peninsula weather is rapidly becoming subtropical due to global warming. In summer 2018, South Korea experienced the highest temperatures since the meteorological observations recorded in 1907. Heat stress has a negative effect on Holstein cows, the most popular breed of dairy cattle in South Korea, which is susceptible to heat. To examine physiological changes in dairy cows under heat stress conditions, we analyzed the profiles circulating microRNAs isolated from whole blood samples collected under heat stress and non-heat stress conditions using small RNA sequencing. We compared the expression profiles in lactating cows under heat stress and non-heat stress conditions to understand the regulation of biological processes in heat-stressed cows. Moreover, we measured several heat stress indicators, such as rectal temperature, milk yield, and average daily gain. All these assessments showed that pregnant cows were more susceptible to heat stress than non-pregnant cows. In addition, we found the differential expression of 11 miRNAs (bta-miR-19a, bta-miR-19b, bta-miR-30a-5p, and several from the bta-miR-2284 family) in both pregnant and non-pregnant cows under heat stress conditions. In target gene prediction and gene set enrichment analysis, these miRNAs were found to be associated with the cytoskeleton, cell junction, vasculogenesis, cell proliferation, ATP synthesis, oxidative stress, and immune responses involved in heat response. These miRNAs can be used as potential biomarkers for heat stress.


Assuntos
MicroRNA Circulante/genética , Resposta ao Choque Térmico/genética , Lactação/genética , Animais , Cruzamento , Bovinos , Doenças dos Bovinos/genética , Feminino , Perfilação da Expressão Gênica/métodos , Transtornos de Estresse por Calor/sangue , Temperatura Alta , MicroRNAs/genética , Leite/metabolismo , Gravidez , RNA Circular/genética , República da Coreia , Estações do Ano , Análise de Sequência de RNA/métodos
11.
Biol Res ; 53(1): 40, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938500

RESUMO

Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.


Assuntos
MicroRNAs , Osteoporose , RNA Circular , RNA Longo não Codificante , Humanos , MicroRNAs/genética , Osteoporose/genética , RNA Circular/genética , RNA Longo não Codificante/genética
12.
Life Sci ; 259: 118269, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798559

RESUMO

BACKGROUND: Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has complex pathogenesis. Circular RNAs (circRNAs) exert broad biological functions on human diseases. This study intended to explore the role and mechanism of circ_WBSCR17 in DN. METHODS: DN mice models were constructed using streptozotocin injection, and DN cell models were assembled using high glucose (HG) treatment in human kidney 2 cells (HK-2). The expression of circ_WBSCR17, miR-185-5p and SRY-Box Transcription Factor 6 (SOX6) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of SOX6 and fibrosis markers were examined by western blot. The release of inflammatory cytokines, cell proliferation and apoptosis, were assessed by enzyme-linked immunosorbent assay (ELISA), cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The predicted interaction between miR-185-5p and circ_WBSCR17 or SOX6 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULT: Circ_WBSCR17 was highly expressed in DN mice models and HG-induced HK-2 cells. Circ_WBSCR17 knockdown or SOX6 knockdown promoted cell proliferation and blocked cell apoptosis, inflammatory responses and fibrosis, while circ_WBSCR17 overexpression or SOX6 overexpression conveyed the opposite effects. MiR-185-5p was a target of circ_WBSCR17 and directly bound to SOX6. MiR-185-5p could reverse the role of circ_WBSCR17 or SOX6. Moreover, the expression of SOX6 was modulated by circ_WBSCR17 through intermediating miR-185-5p. CONCLUSION: Circ_WBSCR17 triggered the dysfunction of HG-induced HK-2 cells, including inflammatory responses and fibrosis, which was accomplished via the miR-185-5p/SOX6 regulatory axis.


Assuntos
Nefropatias Diabéticas/metabolismo , Túbulos Renais/metabolismo , MicroRNAs/metabolismo , N-Acetilgalactosaminiltransferases/genética , RNA Circular/metabolismo , Fatores de Transcrição SOXD/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fibrose/genética , Fibrose/metabolismo , Glucose/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Túbulos Renais/patologia , Túbulos Renais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , N-Acetilgalactosaminiltransferases/metabolismo , RNA Circular/genética , Fatores de Transcrição SOXD/genética
13.
Life Sci ; 259: 118241, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32791147

RESUMO

AIMS: Compelling evidences demonstrate that informative RNAs play essential role in therapy of atherosclerosis. Here, we attempted to study the role of hsa_circ_0000345 (circRSF1) in endothelial cell damage through competing endogenous RNA pathway. MATERIALS AND METHODS: Expression of circRSF1, miRNA-758-3p (miR-758) and cyclin D2 (CCND2) was detected using RT-qPCR and western blotting, and the cross-talk among them was identified using dual-luciferase reporter assay and RNA immunoprecipitation. The low-density lipoprotein cholesterol (LDL-C) level was measured with enzyme-linked immunosorbent assay. Cell growth was measured by MTS assay, flow cytometry and caspase-3 activity assay kit. Migration and tube formation were determined by scratch migration assay and tube formation assay, respectively. KEY FINDINGS: CircRSF1 and CCND2 were downregulated, whereas miR-758 was upregulated in serum of patients with atherosclerosis and oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Moreover, levels of circRSF1, miR-758 and CCND2 were correlated with circulating LDL-C level. Restoring circRSF1 and silencing miR-758 could improve cell viability, tube formation and migration of HAECs under ox-LDL treatment, as well as attenuated apoptotic rate and caspase-3 activity. However, miR-758 upregulation counteracted the promotion of circRSF1 on cell growth, migration and tube formation in ox-LDL-induced HAECs; so did CCND2 deletion on effect of miR-758 silence. Notably, circRSF1 and CCND2 could competitively bound to miR-758, and circRSF1 positively regulated CCND2 expression via miR-758. SIGNIFICANCE: CircRSF1 could protect against ox-LDL-induced endothelial cell injury in vitro via miR-758/CCND2 axis, suggesting circRSF1 as a potential target for the treatment of atherosclerosis.


Assuntos
Aterosclerose/sangue , Ciclina D2/metabolismo , MicroRNAs/sangue , Proteínas Nucleares/genética , RNA Circular/sangue , Transativadores/genética , Adulto , Apoptose/efeitos dos fármacos , Aterosclerose/genética , Aterosclerose/patologia , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina D2/genética , Células Endoteliais/metabolismo , Feminino , Humanos , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Circular/genética , Transdução de Sinais/efeitos dos fármacos
14.
Life Sci ; 259: 118251, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32795540

RESUMO

AIMS: Circular RNAs (circRNAs) are relevant to atherosclerosis progression. However, the role and mechanism of circRNA hsa_circ_0029589 (circ_0029589) in atherosclerosis are not fully understood. This research aims to explore the function and mechanism of circ_0029589 in oxidized low-density lipoprotein (ox-LDL)-caused vascular smooth muscle cells (VSMCs) injury in vitro. MAIN METHODS: VSMCs were challenged via ox-LDL to mimic atherosclerosis-like injury in vitro. Circ_0029589, microRNA-214-3p (miR-214-3p) and stromal interaction molecule 1 (STIM1) abundances were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation was investigated via cell viability, cycle, apoptosis and proliferation-associated protein levels. Cell migration and invasion were assessed via transwell analysis. The relationship between miR-214-3p and circ_0029589 or STIM1 was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. KEY FINDINGS: Circ_0029589 level was enhanced in ox-LDL-challenged VSMCs. Circ_0029589 interference constrained cell proliferation, migration and invasion in ox-LDL-challenged VSMCs. miR-214-3p was targeted by circ_0029589 and miR-214-3p knockdown weakened the suppressive function of circ_0029589 silence on VSMCs proliferation, migration and invasion. STIM1 was targeted via miR-214-3p and miR-214-3p could suppress VSMCs proliferation, migration and invasion via decreasing STIM1. Moreover, circ_0029589 modulated STIM1 level by miR-214-3p. SIGNIFICANCE: Circ_0029589 knockdown repressed proliferation, migration and invasion of VSMCs challenged via ox-LDL by regulating miR-214-3p and STIM1, indicating that circ_0029589 might play important role in atherosclerosis.


Assuntos
Aterosclerose/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Circular/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Apoptose/fisiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Humanos , Lipoproteínas LDL/metabolismo , MicroRNAs/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Molécula 1 de Interação Estromal/genética
15.
Gene ; 763: 145066, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32827686

RESUMO

Diabetes is characterized by changed homeostasis of blood glucose levels, which is associated with various complications, including cardiomyopathy, atherosclerosis, endothelial dysfunction, nephropathy, retinopathy and neuropathy. In recent years, accumulative evidence has demonstrated that circular RNAs are identified as a novel type of noncoding RNAs (ncRNAs) involving in the regulation of various physiological processes and pathologic conditions. Specifically, the emergence of complications response to diabetes is finely controlled by a complex gene regulatory network in which circular RNAs play a critical role. Recently, circular RNAs are emerging as messengers that could influence cellular functions under diabetic conditions. Dysregulation of circular RNAs has been closely linked to the pathophysiology of diabetes-related complications. In this review, we aimed to summarize the current progression and underlying mechanisms of circular RNA in the development of diabetes-related complications. We will also provide an overview of circular RNA-regulated cell communications in different types of cells that have been linked to diabetic complications. We anticipated that the completion of this review will provide potential clues for developing novel circular RNAs-based biomarkers or therapeutic targets for diabetes and its associated complications.


Assuntos
Angiopatias Diabéticas/metabolismo , Nefropatias Diabéticas/metabolismo , Neuropatias Diabéticas/metabolismo , RNA Circular/metabolismo , Animais , Biomarcadores/metabolismo , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/terapia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/terapia , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/terapia , Terapia Genética/métodos , Humanos , Ilhotas Pancreáticas/metabolismo , RNA Circular/genética
16.
Nat Commun ; 11(1): 4076, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796851

RESUMO

Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice. Mechanistically, circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex onto Batf promoter to inhibit Batf expression; this in turn suppresses Il17 expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore, Mbd3-/-Rag1-/- and circKcnt2-/-Rag1-/- mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion of Batf promotes colitis resolution. In summary, our data support a function of the circRNA circKcnt2 in regulating ILC3 inactivation and resolution of innate colitis.


Assuntos
Colite/imunologia , Colite/metabolismo , Linfócitos/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo , RNA Circular/metabolismo , Animais , Colite/patologia , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Homeostase , Humanos , Imunidade Inata , Inflamação/imunologia , Inflamação/patologia , Intestinos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Canais de Potássio Ativados por Sódio/genética , RNA Circular/genética , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Fatores de Transcrição/genética
17.
Gene ; 762: 145057, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32805314

RESUMO

COVID-19 is a lurking calamitous disease caused by an unusual virus, SARS-CoV-2, causing massive deaths worldwide. Nonetheless, explicit therapeutic drugs or clinically approved vaccines are not available for COVID-19. Thus, a comprehensive research is crucially needed to decode the pathogenic tools, plausible drug targets, committed to the development of efficient therapy. Host-pathogen interactions via host cellular components is an emerging field of research in this respect. miRNAs have been established as vital players in host-virus interactions. Moreover, viruses have the capability to manoeuvre the host miRNA networks according to their own obligations. Besides protein coding mRNAs, noncoding RNAs might also be targeted in infected cells and viruses can exploit the host miRNA network via ceRNA effect. We have predicted a ceRNA network involving one miRNA (miR-124-3p), one mRNA (Ddx58), one lncRNA (Gm26917) and two circRNAs (Ppp1r10, C330019G07RiK) in SARS-CoV infected cells. We have identified 4 DEGs-Isg15, Ddx58, Oasl1, Usp18 by analyzing a mRNA GEO dataset. There is no notable induction of IFNs and IFN-induced ACE2, significant receptor responsible for S-protein binding mediated viral entry. Pathway enrichment and GO analysis conceded the enrichment of pathways associated with interferon signalling and antiviral-mechanism by IFN-stimulated genes. Further, we have identified 3 noncoding RNAs, playing as potential ceRNAs to the genes associated with immune mechanisms. This integrative analysis has identified noncoding RNAs and their plausible targets, which could effectively enhance the understanding of molecular mechanisms associated with viral infection. However, validation of these targets is further corroborated to determine their therapeutic efficacy.


Assuntos
Infecções por Coronavirus/genética , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno/genética , Pneumonia Viral/genética , RNA Circular/genética , RNA Longo não Codificante/genética , Animais , Betacoronavirus , Humanos , Camundongos , MicroRNAs/genética , Pandemias , Mapeamento de Interação de Proteínas , RNA Mensageiro/genética
18.
PLoS Pathog ; 16(8): e1008346, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764824

RESUMO

Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.


Assuntos
Carcinoma Hepatocelular/virologia , Hepacivirus/genética , Hepatite C/complicações , Neoplasias Hepáticas/virologia , Provírus/genética , RNA Circular/genética , RNA Viral/genética , Replicação Viral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Perfilação da Expressão Gênica , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Degradação do RNAm Mediada por Códon sem Sentido , Proteínas Virais/genética , Proteínas Virais/metabolismo
19.
Gene ; 762: 145040, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777520

RESUMO

Circular RNAs (circRNA) are a special kind of covalently closed single-stranded RNA molecules. They have been shown to control and coordinate various biological processes. Recent researches show that circRNAs are closely associated with numerous chronic human diseases. Identification of circRNA-disease associations will contribute towards diagnosing the pathogenesis of diseases. Experimental methods for finding the relation between the diseases and their causal circRNAs are difficult and time-consuming. So computational methods are of critical need for predicting the associations between circRNAs and various human diseases. In this study, we propose an ensemble approach AE-DNN, which relies on autoencoder and deep neural networks to predict new circRNA-disease relationships. We utilized circRNA sequence similarity, disease semantic similarity, and Gaussian interaction profile kernel similarities of circRNAs and diseases for feature construction. The constructed features are fed to a deep autoencoder, and the extracted compact, high-level features are fed to the deep neural network for association prediction. We conducted 5-fold and 10-fold cross-validation experiments to assess the performance; AE-DNN could achieve AUC scores of 0.9392 and 0.9431, respectively. Experimental results and case studies indicate the robustness of our model in circRNA-disease association prediction.


Assuntos
Aprendizado Profundo , Predisposição Genética para Doença , RNA Circular/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , RNA Circular/metabolismo
20.
Gene ; 762: 145035, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777531

RESUMO

Circular RNAs belong to the class of endogenous long non-coding RNAs that play important roles in many physiological processes including tumorigenesis. One such process is the onset of colorectal cancers (CRC) which is one of the most prevalent cancers in the world. However, the involvement of the circRNAs in CRC progression is still obscure. In this study, we screened the differentially expressed circRNAs in CRC by taking 10 pairs of tumor and non-tumor transcriptomic data. Datasets were downloaded from EBI ENA database and differential expression analysis was performed. For functional characterization and pathway enrichment of differentially expressed circRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed. Interactions with miRNAs and RNA binding proteins (RBPs) were predicted using miRanda, miRTarBase and starBase tools respectively. Our results identified total of 122 differentially expressed circRNAs in CRC onset, including 85 upregulated and 37 downregulated. GO and KEGG analyses revealed these circRNAs to be involved in many tumorigenic pathways. In addition, we predicted many miRNA and RBP targets of significantly expressed circRNAs that could exhibit the functional role in CRC progression. Combined analyses of miRanda, miRTarBase and KEGG pathway suggested that the possibly affected genes by circRNA-miRNA sponge to be associated with many cancer related pathways. From our findings we concluded 16 novel differentially expressed circRNAs that could play important roles in carcinogenesis of CRC. Our findings provide new insights in circRNA research and could therefore be useful in the development of potential biomarker and therapeutic approaches for CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , RNA Circular/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Circular/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA