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Cardiovascular disease represents the leading cause of death in the world,and early diagnosis and treatment are critical to its prognosis.The lncRNA-taurine up-regulated gene 1(TUG1)mediates a competing endogenous RNA network involved in the development of cardiovascular diseases,involving biological processes such as inflamma-tion,immunity,apoptosis,pyroptosis and oxidative stress.This review summarizes the progress of lncRNA-TUG1 as a competing endogenous RNA to mediate the above biological processes in coronary atherosclerotic heart disease,myocardi-al ischemia-reperfusion injury,heart failure,hypertension,atrial fibrillation and diabetic cardiomyopathy,to provide a reference for subsequent research on cardiovascular diseases.
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Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.
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Objective To investigate the impact of long non-coding RNA(LncRNA)taurine up-regulated gene 1(TUG1)on high glucose-induced cardiomyocyte apoptosis by regulating miR-181b-5p/programmed cell death protein 4(PDCD4)axis.Methods Diabetic cardiomyopathy(DCM)cell model was established in vitro with high glucose(HG,25 mmol/L glucose).AC16 cells were divided into the NG(5.5 mmol/L glucose)group,the HG group,the HG+sh-NC group,the HG+sh-TUG1 group,the HG+miR-NC group,the HG+miR-181b-5p group,the HG+sh-TUG1+anti-miR-NC group,the HG+sh-TUG1+anti-miR-181b-5p group,the HG+miR-181b-5p+pcDNA group and HG+miR-181b-5p+pc-PDCD4 group.The Cell Counting Kit-8(CCK-8)method was applied to detect cell viability.Lactate dehydrogenase(LDH)assay was applied to detect LDH release.Quantitative real-time polymerase chain reaction(qRT-PCR)was applied to detect expression levels of TUG1,miR-181b-5p and PDCD4 mRNA.Flow cytometry was applied to detect apoptosis.Western blot assay was applied to detect levels of B-cell lymphoma 2-associated X(Bax),activated caspase 3(cleaved caspase 3)and PDCD4 proteins.Caspase-Glo3 assay was applied to assess caspase 3 activity.Dual-luciferase reporter assay was applied to verify the targeting relationship between TUG1 or PDCD4 and miR-181b-5p.Results Compared with the NG group,the cell activity decreased in the HG group,and LDH release,apoptosis rate,Bax,cleaved caspase 3 expression and caspase 3 activity increased(P＜0.05),which could be antagonized by TUG1 knockdown or miR-181b-5p overexpression(P＜0.05).Inhibition of miR-181b-5p was able to alleviate the impact of TUG1 silencing on cardiomyocyte viability and apoptosis under high glucose treatment(P＜0.05).The overexpression of PDCD4 attenuated the promotion effect of miR-181b-5p up-regulation on the viability of cardiomyocytes treated with high glucose and the inhibitory effect on apoptosis.TUG1 was able to increase the expression of PDCD4 through adsorption of miR-181b-5p(P＜0.05).Conclusion TUG1 promotes high glucose-induced cardiomyocyte apoptosis by down-regulating miR-181b-5p and up-regulating PDCD4.
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@#Objective: To investigate the expression of lncRNA TUG1 (long non-coding RNA taurine up-regulated gene 1) in gastric cancer and its effect on the proliferation and apoptosis of gastric cancer cells. Methods: Surgically resected gastric cancer tissues and corresponding distal normal tissues (>5 cm away from the margin of tumor) of 40 gastric cancer patients from March 2016 to December 2017 at Ganzhou People's Hospital of Jiangxi Province were collected, and qPCR was used to examine the expression of lncRNA TUG1.AGS gastric cancer cells were transfected with lncRNATUG1 over-expression plasmids and siRNAs, and the effects of lncRNA TUG1 on cell proliferation and apoptosis were assessed by CCK-8, qPCR and Flow cytometry. Results: lncRNATUG1 expression was significantly increased in gastric cancer tissues as compared to normal tissues; and it was not correlated with gender, age, tumor size, infiltration depth of tumor, lymph node-metastasis, tumor differentiation and TNM staging. TUG1 over-expression significantly suppressed the expressions of CDKN1A, BAX and Caspase-3 in AGS gastric cancer cells, and decreased G1 phase proportion and apoptosis rate, but increased S phase proportion and cell viability; in contrast, TUG1 siRNA transfection significantly promoted the expressions of CDKN1A, BAX and Caspase-3, and increased G1 phase proportion and apoptosis rate, but decreased S phase proportion and cell viability. Conclusion: Up-regulated lncRNATUG1 promotes proliferation and inhibits apoptosis of gastric cancer cells.
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Objective To explore the significance of long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in hepatocellular carcinoma (HCC),to predict the target gene of TUG1,and to provide a ref-erence for further study of TUG1 in HCC.Methods The differential expression of TUG1 in HCC was ana-lyzed by using the UALCAN database and the survival analysis of TUG1 was performed.The target gene of TUG1 was predicted by RegRNA 2.0 biology software,HMDD,targetscan and microT-CDS,and the regulato-ry network of lncRNA TUG1-microRNAs-mRNAs was constructed.The predicted target gene was analyzed by Gene Ontology (GO) and KEGG signal transduction pathway enrichment by using FunRich platform. Results TUG1 expression in HCC was significantly increased,and the expression level of TUG1 increased generally with the increase of tumor grade.The overall survival of patients with low expression of lncRNA TUG1 was significantly longer than that of lncRNA TUG1 high expression patients.There were four possible binding sites of HCC related microRNAs (hsa-mir-122-5p,hsa-mir-200a-3p,hsa-mir-34c-3p,hsa-mir-629-3p) on TUG1,which regulated 245 downstream target genes and formed the regulatory network of lncRNA TUG1-microRNAs-mRNAs.In the biological process,microRNA target genes were highly enriched in the processes such as the regulation of nucleobase,nucleoside,nucleotide and nucleic acid metabolism.In KEGG pathway analysis,microRNA target genes were highly enriched to the signal pathways mediated by Syndecan and TRAIL.Conclusion TUG1 expression level in HCC increased.Increased expression of TUG1 is associat-ed with poor prognosis in HCC.Bioinformatics methods can be used to explore the mechanism of tumorigene-sis from the molecular level,which can provide valuable information for subsequent experiments and clinical diagnosis and treatment.
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It has been estimated that approximately 75% of the human genome is transcribed into RNA, 74% of which would be transcribed into non-coding RNA (ncRNA).The ncRNA can be divided into 2 major groups including small RNA and long non-coding RNA (lncRNA).There is increasing evidence that the dysregulation of lncRNA is closely associated with the occurrence and progression of many tumors.The lncRNA taurine up-regulated gene 1 (TUG1) is originally detected in a genomic screen for genes in response to taurine treatment of developing mouse retinal cells.According to research reports, dysregulation of TUG1 participates in the progression of a variety of tumors.Therefore, the regulatory effects of lncRNA TUG1 on tumorigenesis are summarized in this article.
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Objective To detect the expression level of Taurine up?regulated gene 1( TUG1) in the re?nal cell carcinoma and paired paracancerous normal tissues,then explore the relationships between the expression level of TUG1 and clinical characteristics.Methods RNA was Extacted from the resected renal cell carcinoma tissues and paired paracancerous normal tissues of 46 patients respectively,by reverse transcription to get cDNA, the expression level of the TUG1 was detected by RT?qPCR, the relationship between the expression level of TUG1 and the clinicopathological characteristics was analyzed by statistically software. Results The expression of TUG1 in renal cell carcinoma was obviously lower than that in paired paracancerous normal tissues(0.533±0. 027 vs. 1.000±0.298,t=-3.350,P0.05).Conclusion The expression of TUG1 in renal cell carcinoma tissues are down?regulated,which also suggest that it may be re?lated to the tumorigenesis and development of renal cell carcinoma.