BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(X...BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.展开更多
Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the...Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns,across different neurodegenerative diseases.However,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood.This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles,regulatory mechanisms,and research status of lncRNAs in Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Finally,this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases,hoping to provide broader implications for developing effective treatments.展开更多
Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identifi...Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.展开更多
Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-...Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.展开更多
Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still n...Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.展开更多
目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性...目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。展开更多
Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted usin...Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.展开更多
Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome ap...Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.展开更多
Long non-coding RNAs(lncRNAs)are a family of non-protein-coding RNAs that span a length of over 200 nucleotides.Research reports have illustrated that lncRNAs are involved in various cellular processes and that their ...Long non-coding RNAs(lncRNAs)are a family of non-protein-coding RNAs that span a length of over 200 nucleotides.Research reports have illustrated that lncRNAs are involved in various cellular processes and that their abnormal expression leads to the occurrence and development of various tumors.Colon cancer-associated transcript 2(CCAT2)was first reported as an oncogene in colon cancer.LncRNA CCAT2 is abnormally expressed in hepatocellular carcinoma,cholangiocarcinoma,lung cancer,breast cancer,ovarian cancer,glioma,and other tumors.In tumor tissues,abnormally overexpressed CCAT2 can affect cell proliferation,migration,epithelial-mesenchymal transition,apoptosis,and other biological behaviors through endogenous RNAs mechanisms,various signaling pathways,transcriptional regulation,and other complex mechanisms.Additionally,the overexpression of CCAT2 is also closely related to the tumor size,tumor node metastasis(TNM)stage,survival time,and other prognostic factors,suggesting that it is a potential prognostic indicator.This article reviews the biological functions of CCAT2 and its mechanisms of action in tumors from previous studies.In this review,we attempt to provide a molecular basis for future clinical applications of lncRNA CCAT2.展开更多
目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2...目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2020年2月~2021年6月在华北石油管理局总医院诊断为ACS的患者156例,包括不稳定型心绞痛(unstable angina,UA)80例(UA组)和急性心肌梗死(acute myocardial infarction,AMI)76例(AMI组);另选取同期体检健康者100例作为对照组。实时荧光定量PCR法检测受试者血清LncRNA XIST和miR-330-3p水平;24 h动态心电图检测受试者心率变异性(heart rate variability,HRV)时域指标[包括:24 h内正常R-R间期标准差(SDNN)、每5 min R-R间期平均值的标准差(SDANN)、每5 min R-R间期标准差的平均值(SDNN index)、相邻R-R间期之差的均方根(RMSSD)及相邻R-R间期相差>50 ms心搏数占总心搏数的百分比(PNN50)]以及Pearson法分析ACS患者血清LncRNA XIST和miR-330-3p水平与HRV时域指标的相关性。结果与对照组比较,UA组和AMI组血清LncRNA XIST(1.37±0.26,1.69±0.31 vs 1.09±0.22)水平升高(F=113.587,P=0.000),miR-330-3p(0.82±0.15,0.53±0.12 vs 1.03±0.18)及SDANN(115.96±19.57 ms,98.96±16.57 ms vs 133.43±21.01 ms),SDNN(113.84±15.26 ms,101.84±11.22 ms vs 136.41±31.53 ms),SDNN index(54.68±6.72 ms,46.73±5.14 ms vs 64.68±10.64 ms),RMSSD(27.48±5.62 ms,21.37±3.64 ms vs 36.48±8.62 ms)和PNN50(7.58%±2.83%,4.18%±1.13%vs 10.72%±3.21%)水平均降低(F=54.923~225.201,均P=0.000),差异均有统计学意义。与UA组比较,AMI组血清LncRNA XIST水平升高(t=10.792,P<0.05),miR-330-3p及SDANN,SDNN,SDNN index,RMSSD和PNN50水平降低,差异有统计学意义(t=4.743~16.538,均P<0.05);ACS患者血清LncRNA XIST与SDNN index,RMSSD和PNN50呈负相关(r=-0.465,-0.532,-0.542,均P<0.05);miR-330-3p与SDNN index,RMSSD和PNN50呈正相关(r=0.471,0.562,0.561,均P<0.05)。结论ACS患者血清LncRNA XIST水平升高,miR-330-3p水平降低,与心脏自主神经功能有关,可作为防治ACS的重要靶点。展开更多
基金Supported by Natural Science Foundation of Shenzhen University General Hospital (SUGH2020QD011)
文摘BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.
基金supported by the National Natural Science Foundation of China,Nos.91649119 and 92049105(both to JL)。
文摘Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns,across different neurodegenerative diseases.However,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood.This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles,regulatory mechanisms,and research status of lncRNAs in Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Finally,this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases,hoping to provide broader implications for developing effective treatments.
文摘Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.
基金supported by the National Natural Science Foundation of China,No.81600747(to YD)the Start-Up Foundation for Doctors of Liaoning Province,China,No.201501020(to YD)。
文摘Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.
文摘Long non-coding RNAs(lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification(DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing(AS) may play a significant role in the post-transcriptional regulation of lncRNAs.
文摘目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。
基金supported by grants from the National Natural Science Foundation of China(No.81773980)Project of Science and Technology Commission of Shanghai Municipality(No.15401902600)。
文摘Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.
基金provided by the British Heart Foundation,UK(Grant No.CH/15/1/31199)
文摘Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.
基金Anhui Province Science Foundation(No.2008085MH256).
文摘Long non-coding RNAs(lncRNAs)are a family of non-protein-coding RNAs that span a length of over 200 nucleotides.Research reports have illustrated that lncRNAs are involved in various cellular processes and that their abnormal expression leads to the occurrence and development of various tumors.Colon cancer-associated transcript 2(CCAT2)was first reported as an oncogene in colon cancer.LncRNA CCAT2 is abnormally expressed in hepatocellular carcinoma,cholangiocarcinoma,lung cancer,breast cancer,ovarian cancer,glioma,and other tumors.In tumor tissues,abnormally overexpressed CCAT2 can affect cell proliferation,migration,epithelial-mesenchymal transition,apoptosis,and other biological behaviors through endogenous RNAs mechanisms,various signaling pathways,transcriptional regulation,and other complex mechanisms.Additionally,the overexpression of CCAT2 is also closely related to the tumor size,tumor node metastasis(TNM)stage,survival time,and other prognostic factors,suggesting that it is a potential prognostic indicator.This article reviews the biological functions of CCAT2 and its mechanisms of action in tumors from previous studies.In this review,we attempt to provide a molecular basis for future clinical applications of lncRNA CCAT2.
文摘目的检测急性冠脉综合征(acute coronary syndrome,ACS)患者血清长链非编码RNA X染色体失活特异转录物(LncRNA X inactivate-specific transcript,LncRNA XIST)和微小RNA(miR)-330-3p水平,分析二者与心脏自主神经功能的关系。方法选取2020年2月~2021年6月在华北石油管理局总医院诊断为ACS的患者156例,包括不稳定型心绞痛(unstable angina,UA)80例(UA组)和急性心肌梗死(acute myocardial infarction,AMI)76例(AMI组);另选取同期体检健康者100例作为对照组。实时荧光定量PCR法检测受试者血清LncRNA XIST和miR-330-3p水平;24 h动态心电图检测受试者心率变异性(heart rate variability,HRV)时域指标[包括:24 h内正常R-R间期标准差(SDNN)、每5 min R-R间期平均值的标准差(SDANN)、每5 min R-R间期标准差的平均值(SDNN index)、相邻R-R间期之差的均方根(RMSSD)及相邻R-R间期相差>50 ms心搏数占总心搏数的百分比(PNN50)]以及Pearson法分析ACS患者血清LncRNA XIST和miR-330-3p水平与HRV时域指标的相关性。结果与对照组比较,UA组和AMI组血清LncRNA XIST(1.37±0.26,1.69±0.31 vs 1.09±0.22)水平升高(F=113.587,P=0.000),miR-330-3p(0.82±0.15,0.53±0.12 vs 1.03±0.18)及SDANN(115.96±19.57 ms,98.96±16.57 ms vs 133.43±21.01 ms),SDNN(113.84±15.26 ms,101.84±11.22 ms vs 136.41±31.53 ms),SDNN index(54.68±6.72 ms,46.73±5.14 ms vs 64.68±10.64 ms),RMSSD(27.48±5.62 ms,21.37±3.64 ms vs 36.48±8.62 ms)和PNN50(7.58%±2.83%,4.18%±1.13%vs 10.72%±3.21%)水平均降低(F=54.923~225.201,均P=0.000),差异均有统计学意义。与UA组比较,AMI组血清LncRNA XIST水平升高(t=10.792,P<0.05),miR-330-3p及SDANN,SDNN,SDNN index,RMSSD和PNN50水平降低,差异有统计学意义(t=4.743~16.538,均P<0.05);ACS患者血清LncRNA XIST与SDNN index,RMSSD和PNN50呈负相关(r=-0.465,-0.532,-0.542,均P<0.05);miR-330-3p与SDNN index,RMSSD和PNN50呈正相关(r=0.471,0.562,0.561,均P<0.05)。结论ACS患者血清LncRNA XIST水平升高,miR-330-3p水平降低,与心脏自主神经功能有关,可作为防治ACS的重要靶点。
