目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访1...目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。展开更多
BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR...Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms.Methods Thioacetamide(TAA)-and acetaminophen(APAP)-induced ALF mouse models were established,and human samples were collected.The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,or immunochemical staining in miR-29a-3p knock-in transgenic mouse(MIR29A(KI/KI))DIALF models.In addition,RNA sequencing was conducted to explore the mechanisms.Results MiR-29a-3p levels were decreased in TAA-and APAP-induced DIALF models.MiR-29a-3p prevented DIALF caused by TAA and APAP.RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis,and the inhibition was dependent on activation of the PI3K/AKT pathway.In addition,miR-29a-3p levels were reduced,and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients.Conclusion The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF.MiR-29a-3p may be a promising therapeutic target for DIALF.展开更多
Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ...Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ofbreast cancer cells. Methods: The mRNA expression pattern of circHIAT1, miR-19a-3p, and PTEN was checked byreal-time quantitative polymerase chain reaction. Then, the knockdown assay was carried out to explore the effect ofcircHIAT1 and miR-19a-3p on breast cancer. The relative cell experiments, including MTT assay, scratch assay,transwell invasion assay, and flow cytometry analysis, were conducted to verify the influence of circHIAT1 and miR-19a-3p on breast cancer cells. Results: The levels of PTEN and circHIAT1 were reduced, while that of miR-19a-3pwas elevated in breast cancer tissues and cells. MiR-19a-3p was proved to be the target gene of circHIAT1 via a dualluciferase experiment, which could also modulate the PTEN mRNA level. Overexpression of circHIAT1 was able toundermine the growth, migratory ability, and invasiveness in breast cancer cells, which could be antagonized by miR-19a-3p mimic. The inhibition of miR-19a-3p in vitro also impaired the malignancy of breast cancer, which dependedon the modulation of PTEN expression. Conclusion: CircHIAT1 controls the PTEN expression level in cells of breastcancer by negatively regulating miR-19a-3p. This mechanism controls the growth, invasion, and migration of breastcancer.展开更多
文摘目的探究血清microRNA-21(miR-21)、microRNA-193a-3p(miR-193a-3p)水平与结直肠癌患者手术预后的关系。方法回顾性分析2020年1月—2022年1月苏州大学附属第一医院收治112例结直肠癌患者的病历资料。患者均接受结直肠癌根治术,术后随访16个月,记录患者的预后生存结局,多因素逐步Logistic回归分析结直肠癌患者手术预后的影响因素,评估血清miR-21、miR-193a-3p对结直肠癌患者预后的预测效能。结果112例结直肠癌患者死亡22例,病死率为19.64%;生存90例,生存率为80.36%。死亡组术前血清miR-21 mRNA相对表达量、临床分期Ⅲ期占比、淋巴结转移率均高于生存组(P<0.05),血清miR-193a-3p m RNA相对表达量低于生存组(P<0.05)。多因素逐步Logistic回归分析结果显示,临床分期Ⅲ期[OR=3.777(95%CI:1.399,10.194)]、淋巴结转移[OR=5.099(95%CI:1.715,15.156)]、miR-21表达升高[OR=4.889(95%CI:1.645,14.533)]、miR-193a-3p表达降低[OR=4.402(95%CI:1.481,13.084)]均是直肠癌患者预后的影响因素(P<0.05)。受试者工作特性曲线分析结果显示,血清miR-21、miR-193a-3p单一及联合预测结直肠癌预后的敏感性分别为69.04%(95%CI:0.487,0.813)、72.73%(95%CI:0.495,0.884)、86.36%(95%CI:0.640,0.964),特异性分别为62.22%(95%CI:0.513,0.720)、68.89%(95%CI:0.581,0.780)、90.00%(95%CI:0.814,0.950),曲线下面积分别为0.782、0.731和0.901。结论结直肠癌患者术前miR-21、miR-193a-3p表达与术后预后密切相关,且在结直肠癌患者的预后结局中表现出良好的预测效能。
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
基金This project was supported by grants from the National Science and Technology Major Project(No.2014ZX10005001 and No.2018ZX10302204-001)Chen Xiaoping Development Foundation(No.CXPJJH12000002-2020032).
文摘Objective Little is known about the role of microRNA-29a-3p(miR-29a-3p)in inflammation-related pyroptosis,especially in drug-induced acute liver failure(DIALF).This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms.Methods Thioacetamide(TAA)-and acetaminophen(APAP)-induced ALF mouse models were established,and human samples were collected.The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,or immunochemical staining in miR-29a-3p knock-in transgenic mouse(MIR29A(KI/KI))DIALF models.In addition,RNA sequencing was conducted to explore the mechanisms.Results MiR-29a-3p levels were decreased in TAA-and APAP-induced DIALF models.MiR-29a-3p prevented DIALF caused by TAA and APAP.RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis,and the inhibition was dependent on activation of the PI3K/AKT pathway.In addition,miR-29a-3p levels were reduced,and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients.Conclusion The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF.MiR-29a-3p may be a promising therapeutic target for DIALF.
基金All experimental procedures were conducted in accordance with Animal Ethics Procedures and Guidelines of the Animal Center,Yunnan University Animal Ethics Committee(Ethics Review Number:YNU20220296).
文摘Objective: Breast cancer is a major cancer threatening the health of women globally. To elucidate the effect ofthe circHIAT1/miR-19a-3p/phosphatase and tensin homolog (PTEN) axis on regulating the malignant phenotype ofbreast cancer cells. Methods: The mRNA expression pattern of circHIAT1, miR-19a-3p, and PTEN was checked byreal-time quantitative polymerase chain reaction. Then, the knockdown assay was carried out to explore the effect ofcircHIAT1 and miR-19a-3p on breast cancer. The relative cell experiments, including MTT assay, scratch assay,transwell invasion assay, and flow cytometry analysis, were conducted to verify the influence of circHIAT1 and miR-19a-3p on breast cancer cells. Results: The levels of PTEN and circHIAT1 were reduced, while that of miR-19a-3pwas elevated in breast cancer tissues and cells. MiR-19a-3p was proved to be the target gene of circHIAT1 via a dualluciferase experiment, which could also modulate the PTEN mRNA level. Overexpression of circHIAT1 was able toundermine the growth, migratory ability, and invasiveness in breast cancer cells, which could be antagonized by miR-19a-3p mimic. The inhibition of miR-19a-3p in vitro also impaired the malignancy of breast cancer, which dependedon the modulation of PTEN expression. Conclusion: CircHIAT1 controls the PTEN expression level in cells of breastcancer by negatively regulating miR-19a-3p. This mechanism controls the growth, invasion, and migration of breastcancer.
