目的探讨血液透析治疗对血清中microRNA-92a的去除效果及其损伤内皮细胞功能的机制。方法收集西安高新医院长期透析治疗的慢性肾病患者,分别收集透析前、透析后6 h左右血清,测定其中miR-92a含量变化,同时测定BUN、Scr及hsCRP水平变化。...目的探讨血液透析治疗对血清中microRNA-92a的去除效果及其损伤内皮细胞功能的机制。方法收集西安高新医院长期透析治疗的慢性肾病患者,分别收集透析前、透析后6 h左右血清,测定其中miR-92a含量变化,同时测定BUN、Scr及hsCRP水平变化。培养的内皮细胞给予慢性肾脏病患者透析前后血清刺激,观察miR-92a及其靶基因eNOS表达变化。结果透析前后血清中miR-92a含量(1.48±0.24 vs 1.20±0.18,P=0.356)及hsCRP(7.6±2.4 vs 7.5±3.1,P=0.862)水平无显著差异。而透析治疗可显著降低血清中BUN(26.4±8.8 vs 8.3±2.3,P<0.01)、Scr(926.3±178.1 vs 312.3±141.2,P<0.01)水平。进一步体外细胞实验RT-PCR检测证实与健康人血清相比,慢性肾脏病患者透析前后血清均可促使培养的脐静脉内皮细胞miR-92a表达增加(P<0.01),RT-PCR及Western Blot检测证实其靶基因eNOS表达均显著降低(P<0.01),内皮细胞功能受损。结论血液透析治疗前后血清中miR-92a下降不明显,miR-92a可致内皮细胞eNOS表达减少,这可能是透析治疗虽然能维持肾脏功能但是无法避免其心血管并发症发生的部分原因。展开更多
Background:Stool-based molecular markers have shown potential as a strategy for colorectal cancer(CRC)screening.This study aimed to evaluate the feasibility of using microRNA-92a expression as a biomarker for CRC in s...Background:Stool-based molecular markers have shown potential as a strategy for colorectal cancer(CRC)screening.This study aimed to evaluate the feasibility of using microRNA-92a expression as a biomarker for CRC in stool samples.Methods:The level of microRNA-92a was measured in stool samples from 210 CRC patients,29 patients with advanced adenomas,15 patients with other cancers,and 101 healthy controls,using real-time quantitative polymerase chain reaction.Receiver operating characteristic curves were used to evaluate sensitivity and specificity.Results:MicroRNA-92a expression was positive in 70.1%of CRC patients,44.8%of advanced adenomas patients,and 36.6%of healthy controls,using a cut-off value of 31.5.The corresponding sensitivity and specificity for discriminating CRC from advanced adenomas were 66.9%and 63.4%,respectively.Moreover,stool-based microRNA-92a expression was better at detecting CRC cancers in the distal colon(sensitivity 82.1%)than the proximal colon(sensitivity 67.9%).There were no significant differences in clinical stage of CRC when comparing AUCs of each parameter(P>0.05).Conclusion:These findings suggest that microRNA-92a expression in stool samples could serve as a promising non-invasive biomarker for CRC detection.展开更多
Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in ...Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. Aim: To assess the plasma level of microRNA-92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on fifty AML patients as well as fifty healthy subjects as control. Conventional cytogenetics was performed on patients group only while measurement of the plasma level of miRNA-92a using TaqMan quantitative RT-PCR with miRNA-638 as endogenous reference for standardization and FLT3/ITD mutation was performed on patients and controls. Results: The differences in the ratio or relative quantitation (RQ) of plasma miRNa-92a to miRNA-638 in patients group to the control group have confirmed statistical significance. Also there was significant negative correlation between RQ of miRNA-92a and white blood count in patient group. Patients who achieved a response after induction chemotherapy had a mean RQ of miRNA-92a higher than non-responder with statistical significance. With regard to cytogenetics, favorable risk cytogenetics had meant RQ of miRNA-92a that was comparable to intermediate risk cytogenetics. While poor risk cytogenetics had a mean RQ which is significantly lower than both favorable and intermediate risk cytogenetics. Summary/Conclusions: Our data suggest the potential importance of the microRNA-92a as noninvasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.展开更多
目的探究miR-92a-3p靶向双特异性蛋白磷酸酶1(dual-specificity protein phosphatase 1,DUSP1)在子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)发生发展过程中的功能及内在分子机制。方法运用生物信息学分析策略,从数据库中...目的探究miR-92a-3p靶向双特异性蛋白磷酸酶1(dual-specificity protein phosphatase 1,DUSP1)在子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)发生发展过程中的功能及内在分子机制。方法运用生物信息学分析策略,从数据库中筛选鉴定出miR-92a-3p在UCEC组织及细胞系中存在显著差异的表达模式,并预测其潜在的靶基因。将人工合成的miR-92a-3p模拟物及其对应的阴性对照转染至人UCEC细胞系Ishikawa细胞及HEC-1A细胞,采用Cell Counting Kit-8(CCK-8)法精确测定各组细胞的增殖活性变化;利用Transwell小室实验评估细胞的迁移和侵袭能力;通过实时荧光定量逆转录聚合酶链反应(qRT-PCR)、Western blotting以及双荧光素酶报告基因检测系统,系统阐释miR-92a-3p对DUSP1的基因表达调控关系。构建DUSP1过表达载体并转染至UCEC细胞,借助脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)以及透射电子显微镜技术,观察UCEC细胞的凋亡形态学特征及凋亡相关指标变化。结果生物信息学分析结果显示,在UCEC组织中miR-92a-3p呈现低表达状态,且经预测及后续实验证实DUSP1为miR-92a-3p的直接作用靶点。功能学实验结果表明,miR-92a-3p的过表达能够抑制Ishikawa细胞及HEC-1A细胞的增殖活力,有效减弱细胞的迁移和侵袭潜能。qRT-PCR、Western blotting和双荧光素酶报告基因实验结果共同表明,DUSP1的表达受到miR-92a-3p的负向调控。此外,在UCEC细胞中过表达DUSP1可诱导细胞发生凋亡,呈现出典型的凋亡形态学特征。结论miR-92a-3p可能通过抑制其靶基因DUSP1的转录和翻译过程,进而影响细胞的增殖、迁移、侵袭和凋亡等生物学行为,在UCEC的恶性进展过程中可能发挥重要作用。展开更多
文摘目的探讨血液透析治疗对血清中microRNA-92a的去除效果及其损伤内皮细胞功能的机制。方法收集西安高新医院长期透析治疗的慢性肾病患者,分别收集透析前、透析后6 h左右血清,测定其中miR-92a含量变化,同时测定BUN、Scr及hsCRP水平变化。培养的内皮细胞给予慢性肾脏病患者透析前后血清刺激,观察miR-92a及其靶基因eNOS表达变化。结果透析前后血清中miR-92a含量(1.48±0.24 vs 1.20±0.18,P=0.356)及hsCRP(7.6±2.4 vs 7.5±3.1,P=0.862)水平无显著差异。而透析治疗可显著降低血清中BUN(26.4±8.8 vs 8.3±2.3,P<0.01)、Scr(926.3±178.1 vs 312.3±141.2,P<0.01)水平。进一步体外细胞实验RT-PCR检测证实与健康人血清相比,慢性肾脏病患者透析前后血清均可促使培养的脐静脉内皮细胞miR-92a表达增加(P<0.01),RT-PCR及Western Blot检测证实其靶基因eNOS表达均显著降低(P<0.01),内皮细胞功能受损。结论血液透析治疗前后血清中miR-92a下降不明显,miR-92a可致内皮细胞eNOS表达减少,这可能是透析治疗虽然能维持肾脏功能但是无法避免其心血管并发症发生的部分原因。
基金This study was supported by the National Natural Science Foundation of China(Grant No.82202907 to Rong-Bin Liu).
文摘Background:Stool-based molecular markers have shown potential as a strategy for colorectal cancer(CRC)screening.This study aimed to evaluate the feasibility of using microRNA-92a expression as a biomarker for CRC in stool samples.Methods:The level of microRNA-92a was measured in stool samples from 210 CRC patients,29 patients with advanced adenomas,15 patients with other cancers,and 101 healthy controls,using real-time quantitative polymerase chain reaction.Receiver operating characteristic curves were used to evaluate sensitivity and specificity.Results:MicroRNA-92a expression was positive in 70.1%of CRC patients,44.8%of advanced adenomas patients,and 36.6%of healthy controls,using a cut-off value of 31.5.The corresponding sensitivity and specificity for discriminating CRC from advanced adenomas were 66.9%and 63.4%,respectively.Moreover,stool-based microRNA-92a expression was better at detecting CRC cancers in the distal colon(sensitivity 82.1%)than the proximal colon(sensitivity 67.9%).There were no significant differences in clinical stage of CRC when comparing AUCs of each parameter(P>0.05).Conclusion:These findings suggest that microRNA-92a expression in stool samples could serve as a promising non-invasive biomarker for CRC detection.
文摘Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. Aim: To assess the plasma level of microRNA-92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on fifty AML patients as well as fifty healthy subjects as control. Conventional cytogenetics was performed on patients group only while measurement of the plasma level of miRNA-92a using TaqMan quantitative RT-PCR with miRNA-638 as endogenous reference for standardization and FLT3/ITD mutation was performed on patients and controls. Results: The differences in the ratio or relative quantitation (RQ) of plasma miRNa-92a to miRNA-638 in patients group to the control group have confirmed statistical significance. Also there was significant negative correlation between RQ of miRNA-92a and white blood count in patient group. Patients who achieved a response after induction chemotherapy had a mean RQ of miRNA-92a higher than non-responder with statistical significance. With regard to cytogenetics, favorable risk cytogenetics had meant RQ of miRNA-92a that was comparable to intermediate risk cytogenetics. While poor risk cytogenetics had a mean RQ which is significantly lower than both favorable and intermediate risk cytogenetics. Summary/Conclusions: Our data suggest the potential importance of the microRNA-92a as noninvasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.
