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Objective To analyze the relationship between serum long chain non coding ribonucleic acid(ln-cRNA)ANRIL,microRNA(miR)-423-5p and airway inflammation and remodeling in children with bronchial asthma and its predictive value.Methods A total of 98 children with bronchial asthma treated in Haikou Ma-ternal and Child Health Hospital from June 2020 to December 2022 were selected.46 children with acute at-tack were selected as the attack group and 52 children with clinical remission were selected as the remission group.Another 50 children who were healthy during physical examination in the same period were selected as the health group.The relative expression levels of serum lncRNA ANRIL and miR-423-5p were detected by real-time fluorescence quantitative polymerase chain reaction.The serum inflammatory factor indicators[in-terleukin-13(IL-13),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)]were detected by enzyme-linked immunosorbent assay.Airway remodeling indicators[bronchial thickness(T/D),pipe wall area/total cross-sectional area of gas pipeline(WA)]and lung function indicators[first second forced expiratory volume(FEV1),peak expiratory flow(PEF),maximum mid expiratory flow(MMEF)]were measured.The correlation between expression of serum lncRNA ANRIL,miR-423-5p and airway inflam-mation and remodeling indicators were analyzed by the Pearson method.The predictive value of serum ln-cRNA ANRIL and miR-423-5p in the diagnosis of bronchial asthma was analyzed by receiver operating charac-teristic(ROC)curve.Results The relative expression level of serum lncRNA ANRIL in remission and attack groups was higher than that in healthy group,and the relative expression level of serum miR-423-5p was lower than that in healthy group,with statistical significance(P＜0.05).The relative expression level of serum ln-cRNA ANRIL in the attack group was higher than that in the remission group,and the relative expression lev-el of serum miR-423-5p was lower than that in the remission group,with statistical significance(P＜0.05).The levels of serum VEGF,IL-13 and TGF-β1 in attack and remission groups were higher than those in healthy group,and the difference was statistically significant(P＜0.05).The levels of serum VEGF,IL-13 and TGF-β1 in attack group were higher than those in remission group,and the difference was statistically sig-nificant(P＜0.05).The levels of T/D and WA in the remission and attack groups were higher than those in the healthy group,and the levels of FEV,,PEF and MMEF were lower than those in the healthy group,with statistical significance(P＜0.05).The levels of T/D and WA in the attack group were higher than those in the remission group,and the levels of FEV1,PEF and MMEF were lower than those in the remission group,with statistical significance(P＜0.05).The results of Pearson correlation analysis showed that serum ln-cRNA ANRIL expression was positively correlated with airway inflammation and remodeling indicators,and negatively correlated with lung function indicators(P＜0.05).The expression of miR-423-5p was negatively correlated with airway inflammation and remodeling indexes,and positively correlated with lung function inde-xes(P＜0.05).ROC curve analysis showed that the area under the curve of lncRNA ANRIL and miR-423-5p alone and combined detection were 0.772,0.707 and 0.865 respectively,the predictive value of combined de-tection in diagnosing bronchial asthma was higher.Conclusion The relative expression level of serum lncRNA ANRIL increase in children with bronchial asthma,and miR-423-5p decrease,which promote airway inflamma-tion,remodeling,lung function decrease,and which has high diagnostic efficacy for children with bronchial asthma.
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Abstract Introduction: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Non-coding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. Methods: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. Results: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. Discussion: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.
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Objective:To study the associations between single-nucleotide polymorphisms (SNPs) of rs4977574/rs1537378 in ANRIL gene and risk of ischemic stroke. Methods:PubMed, Embase, The Cochrane Library, and CNKI, Wanfang, and VIP Data were searched from inception to September 2020 to collect literatures about randomized controlled trials on associations between SNPs of rs4977574/rs1537378 in ANRIL gene and risk of ischemic stroke. According to inclusion and exclusion criteria, the literatures were selected and the data were extracted; Stata15.1 software was used for Meta analysis of the literatures. Results:About the associations between rs4977574 polymorphism of ANRIL gene and risk of ischemic stroke, a total of 7 articles were chosen, including 12 553 patients in the case group and 15 547 patients in the control group; about the associations between rs1537378 polymorphism of ANRIL gene and risk of ischemic stroke, a total of 6 articles were chosen, including 6166 patients in case group and 6129 patients in control group. The results of Meta analysis indicated that rs4977574 polymorphism had a significant association with ischemic stroke susceptibility under 5 genetic models: allele model [G vs. A]: OR=1.110, 95%CI: 1.020-1.210, P=0.010; dominance model ([GG+GA] v s. AA): OR=1.170, 95%CI: 1.070-1.280, P=0.001; recessive model (GG vs. [GA+AA]): OR=1.160, 95%CI: 1.050-1.280, P=0.020; homozygote model (GG vs. AA): OR=1.260, 95%CI: 1.130-1.420, P=0.000; heterozygote model (GA vs. AA): OR=1.130, 95%CI: 1.030-1.240, P=0.010. The rs1537378 polymorphism was associated with reduced risk of ischemic stroke under 5 genetic models: allele model (T vs. C): OR=0.800, 95%CI: 0.700-0.920, P=0.001; dominance model ([TT+TC] vs. CC): OR=0.790, 95%CI: 0.680-0.920, P=0.002; recessive model (TT vs. [TC+CC]): OR=0.830, 95%CI: 0.740-0.930, P=0.001; homozygote model (TT vs. CC): OR=0.780, 95%CI: 0.690-0.880, P=0.000; heterozygote model (TC vs. CC): OR=0.870, 95%CI: 0.810-0.940, P=0.001. Conclusions:The rs4977574 polymorphism in ANRIL gene is a susceptibility factor for ischemic stroke, and allele G of this locus can significantly increase the risk of ischemic stroke. The rs1537378 polymorphism in ANRIL gene is a protective factor for ischemic stroke, and carrying this allele T can reduce the risk of ischemic stroke.
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Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.
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Objective To evaluate the correlation of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) with disease risk and severity of bronchial asthma as well as plasma microRNA (miRNA)-125a expression in child patients. Methods Seventy children with asthma exacerbation, 70 children with asthma remission and 70 matched healthy controls were consecutively enrolled in this study. Laboratory parameters and lung function indexes of the participants were recorded. LncRNA ANRIL and miRNA-125a expression levels in plasma were determined using qRT-PCR. Tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and IL-17 levels in plasma were determined using enzyme-linked immunosorbent assay (ELISA). Results LncRNA ANRIL expression was the highest in the asthma exacerbation children, followed by asthma remission children and healthy controls. There were significant differences in the expression of lncRNA ANRIL among the three groups (all P<0.01). Receiver operating characteristic curves revealed that lncRNA ANRIL could well differentiate the participants in the three groups. In the children with asthma exacerbation, lncRNA ANRIL expression was associated with disease severity (P=0.001), positively associated with the levels of TNF-α, IL-1β, IL-6 and IL-17 (all P<0.05), while negatively associated with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and FEV1 as percentage of predicted (FEV1%Pred) value (both P<0.05). LncRNA ANRIL expression was also positively associated with the levels of TNF-α, IL-1β and IL-17 in the asthma remission children and IL-6 level in healthy controls (all P<0.05). LncRNA ANRIL expression was negatively associated with miRNA-125a expression in all the participants (all P<0.05). Besides, miRNA-125a expression was positively correlated with FEV1/FVC and FEV1%Pred value in the children with asthma exacerbetion (both P<0.001). Conclusion LncRNA ANRIL may serve as a novel biomarker for predicting asthma, asthma acute exacerbation and severity, and inflammation level. It may participate in the development and progression of asthma in children via targeting miRNA-125a..
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BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.
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Humanos , Traumatismo por Reperfusão/metabolismo , Hipóxia Encefálica/metabolismo , MicroRNAs/fisiologia , MicroRNAs/genética , RNA Circular , Oxigênio , Encéfalo , Apoptose , Inibidor p16 de Quinase Dependente de Ciclina , Células Endoteliais , RNA Longo não Codificante , Glucose/metabolismo , InflamaçãoRESUMO
Objective@#To investigate the effect and mechanism of LncRNA ANRIL on the radiosensitivity of HCT116 cells line and nude mouse transplant tumors.@*Methods@#The expression of LncRNA ANRIL in colorectal cancer cells was detected by qPCR. The negative control siRNA, ANRIL siRNA, miR-NC mimic, miR-195 mimic, miR-NC inhibitor and miR-195 inhibitor were transfected into HCT116 cells, and marked as negative control group, silencing ANRIL group, overexpressing miR-NC group, overexpressing miR-195 group, inhibiting miR-NC group and inhibiting miR-195 group, and the HCT116 cells without any treatment were marked as the blank control group. The clone formation assay was used to detect radiosensitivity of colorectal cancer cells, flow cytometry was used to detect apoptosis. The web site, StarBase, was used to predict the downstream miRNAs of ANRIL and dual luciferase reporter gene assay was used to further verify. Subcutaneous tumor transplantation assay was used to detect the effect of ANRIL on the growth of colorectal cancer cells after irradiation.@*Results@#After irradiation with 2, 4, 6 and 8 Gy, the cell survival fraction of silencing ANRIL group was significantly decreased when compared with that of negative control group (P<0.05), and the radiosensitivity ratio was 1.52. The apoptosis rate of the silencing ANRIL+ 4 Gy group was significantly higher than that of the negative control+ 4 Gy group ((27.86±2.78)% vs. (12.06±1.46)%, P<0.05). The results of the experiment on nude mouse transplant tumors showed that the tumor volume in the negative control group was lower than that of the silent ANRIL group on days 13, 16, 19, 22 and 25 ((234±66) mm3, (273±63) mm3, (296±72) mm3, (321±85) mm3 and (403±94) mm3 vs. (357±79) mm3, (485±124) mm3, (617±143) mm3, (764±174) mm3 and (985±221) mm3P<0.05). MiR-195 is a target gene of ANRIL, and inhibition of miR-195 can reverse the inhibitory effect of silencing ANRIL on radiosensitivity, apoptosis and xenografts of HCT116 cells.@*Conclusions@#LncRNA ANRIL regulates the radiosensitivity of colorectal cancer cells by miR-195, which may provide a new sensitizing target for clinical colorectal cancer radiotherapy.
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This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731-0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/diagnóstico , RNA Longo não Codificante/genética , Prognóstico , Sedimentação Sanguínea , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/sangue , Proteína C-Reativa/análise , Análise de Sobrevida , Citocinas/sangue , Medição de Risco , Estenose Coronária/complicações , Inflamação/diagnósticoRESUMO
Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) has been reported to promote tumorigenesis via regulating microRNA (miR)-99a in gastric cancer cells. However, the role of each component involved in it is still not well understood. This study aimed to verify the role of ANRIL in gastric cancer as well as the underlying mechanisms. ANRIL levels in clinical gastric cancer tissues and cell lines were tested by qPCR. Effects of ANRIL silence on cell viability, migration and invasion, apoptosis, and miR-99a expression in MKN-45 and SGC-7901 cells were measured using CCK-8, Transwell assay, flow cytometry, and qPCR assays, respectively. Then, effects of miR-99a inhibition on ANRIL-silenced cells were evaluated. B-lymphoma Mo-MLV insertion region 1 (BMI1) expression, after abnormal expression of ANRIL and miR-99a, was determined. Finally, expression of key proteins in the apoptotic, Notch, and mTOR pathways was assessed. ANRIL level was elevated in gastric cancer tissues and cell lines. Knockdown of ANRIL suppressed cell viability, migration, and invasion, and increased apoptosis through up-regulating miR-99a. Furthermore, ANRIL silence down-regulated BMI1 via up-regulating miR-99a. BMI1 silence down-regulated Bcl-2 and key kinases in the Notch and mTOR pathways and up-regulated p16 and cleaved caspases. We verified the tumor suppressive effects of ANRIL knockdown in gastric cancer cells via crosstalk with miR-99a. Together, we provided a novel regulatory mechanism for ANRIL in gastric cancer, in which ANRIL silence down-regulated BMI1 via miR-99a, along with activation of the apoptotic pathway and inhibition of the Notch and mTOR pathways.
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Humanos , Neoplasias Gástricas/metabolismo , Regulação para Baixo , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/metabolismo , RNA Longo não Codificante/genética , Carcinogênese/genética , Neoplasias Gástricas/patologia , Transfecção , Regulação Neoplásica da Expressão Gênica , Regulação para Cima , Apoptose/genética , Linhagem Celular Tumoral , Invasividade NeoplásicaRESUMO
The antisense transcript long non-coding RNA (1ncRNA) (antisense non-coding RNA in the INK4 locus,ANRIL) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on chromosome 9p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame (ARF).In the context of gene regulation,ANRIL is responsible for directly recruiting polycomb group (PcG) proteins,including polycomb repressive complex-1 (PRC-1) and polycomb repressive complex-2 (PRC-2),to modify the epigenetic chrornatin state and subsequently inhibit gene expression in cis-regulation.On the other hand,previous reports have indicated that ANRIL is capable of binding to a specific site or sequence,including the Alu element,E2F transcription factor 1 (E2F1),and CCCTC-binding factor (CTCF),to achieve trans-regulation functions.In addition to its function in cell proliferation,adhesion and apoptosis,ANRIL is very closely associated with atherosclerosis-related diseases.The different transcripts and the SNPs that are related to atherosclerotic vascular diseases (ASVD-SNPs) are inextricably linked to the development and progression of atherosclerosis.Linear transcripts have been shown to be a risk factor for atherosclerosis,whereas circular transcripts are protective against atherosclerosis.Furthermore,ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation,which is considered to be one of the causes of atherosclerosis.Collectively,ANRIL plays an important role in the formation of atherosclerosis,and the artificial modification of ANRIL transcripts should be considered following the development of this disease.
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Long non-coding RNAs are important regulators of gene expression.ANRIL which was coded on the Chr9p21.3 loci participates in the pathogenesis of tumor, coronary artery disease, type 2 diabetes mellitus and oth-er diseases.Multiple ANRIL isoforms are tissue-specific.ANRIL mainly functions through Polycomb proteins, while there are also other downstream targets.The mechanism of each isoform and the downstream pathways are hotspots incurrent researches.