目的:低风险微小乳头状甲状腺癌(papillary thyroid carcinoma,PTC)的检出增加与过度诊断和治疗有关。N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)修饰导致的微RNA(microRNAs,miRNA)失调在肿瘤转移和进展中发挥重要作用。然而,m^(6)...目的:低风险微小乳头状甲状腺癌(papillary thyroid carcinoma,PTC)的检出增加与过度诊断和治疗有关。N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)修饰导致的微RNA(microRNAs,miRNA)失调在肿瘤转移和进展中发挥重要作用。然而,m^(6)A靶向miRNAs在PTC中的功能仍不清楚。本研究旨在探究m^(6)A-miR-139-5p在PTC中的表达调控机制,明确其与PTC转移的关联,并评估其作为PTC转移诊断生物标志物的潜力,为PTC的精准诊断和治疗提供实验依据。方法:通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)和GSE130512队列筛选与PTC转移相关的候选靶向m^(6)A-miRNA分子。收集13例PTC转移患者和18例非转移患者的临床标本,检测m^(6)A-miR-139-5p的表达水平,分析其与转移的相关性。通过实验探究脂肪质量和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)对pri-miR-139甲基化水平及加工过程的影响,明确其对miR-139-5p表达的调控作用。在TPC-1细胞中,通过四甲基偶氮唑盐(methyl thiazolyl tetrazolium,MTT)实验检测miR-139-5p过表达对FTO过表达介导的细胞增殖的影响。通过细胞侵袭实验验证miR-139-5p对PTC细胞侵袭能力的作用,并探究其是否通过靶向ZEB1/E-钙黏蛋白轴发挥功能。结果:通过比较TCGA和GSE130512队列,发现血清循环m^(6)A-miR-139-5p可作为检测PTC转移的生物指标。对13例转移和18例非转移临床标本的检测表明,FTO通过降低其甲基化水平抑制pri-miR-139的加工,导致miR-139-5p在PTC中表达失调(P<0.05)。在TPC-1细胞中,MTT实验显示miR-139-5p过表达可部分逆转FTO过表达介导的细胞增殖(P<0.05)。此外,miR-139-5p通过靶向ZEB1/E-钙黏蛋白轴抑制PTC细胞的侵袭能力,而FTO过表达可部分削弱这种抑制效应。结论:血清循环miR-139-5p可作为评估PTC转移的潜在标志物,FTO通过调控pri-miR-139的m^(6)A修饰影响miR-139-5的表达及功能,但其临床价值需进一步验证。展开更多
目的探讨急性脑梗死(ACI)患者血清微小RNA-214(miR-214)的表达水平及其临床意义。方法选取2024年1月~2024年2月濮阳市安阳地区医院收治的ACI患者90例设为ACI组,选取同期健康体检者90例为对照组,比较两组血清miR-214水平,使用受试者工作...目的探讨急性脑梗死(ACI)患者血清微小RNA-214(miR-214)的表达水平及其临床意义。方法选取2024年1月~2024年2月濮阳市安阳地区医院收治的ACI患者90例设为ACI组,选取同期健康体检者90例为对照组,比较两组血清miR-214水平,使用受试者工作特征(ROC)曲线分析血清miR-214水平对ACI的诊断价值。根据入院24 h美国国立卫生研究院卒中量表(NIHSS)评分将ACI患者分为轻度组(n=44)和中重度组(n=46),比较两组血清miR-214水平和入院24 h NIHSS评分及其相关性。根据发病90 d改良Ranking量表(mRS)评分将ACI患者分为预后良好组(n=40)和预后不良组(n=50),比较两组血清miR-214水平和发病90 d mRS评分及其相关性。比较ACI组和对照组血清炎症因子水平,分析ACI患者血清miR-214表达水平及其与炎症因子水平的相关性。结果ACI组血清miR-214水平低于对照组(P<0.05)。ROC曲线结果显示,血清miR-214对ACI诊断的曲线下面积(AUC)为0.968,最佳截断值为0.71,灵敏度为96.67%,特异度为87.78%。中重度组血清miR-214水平较轻度组更低,NIHSS评分更高(P<0.05);ACI患者血清miR-214水平与NIHSS评分呈负相关性(r=-0.759,P<0.05)。预后不良组血清miR-214水平较预后良好组更低,mRS评分更高(P<0.05);ACI患者血清miR-214水平与mRS评分呈负相关性(r=-0.249,P<0.05)。ACI组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)及中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平均高于对照组(P<0.05);ACI患者血清miR-214表达水平与血清IL-6、TNF-α、CRP及NGAL水平均呈负相关性(P<0.05)。结论ACI患者血清miR-214表达水平异常下降,对ACI具有较高诊断价值,且其与ACI病情严重程度、预后及炎症因子水平均呈负相关性,可能会影响疾病进展。展开更多
目的:探讨血清微小RNA(microRNA,miRNA)在结直肠癌诊断中的价值。方法:通过miRNA表达谱芯片检测7例结直肠癌患者血清和10例健康志愿者血清中差异表达的miRNA。应用实时荧光定量PCR法在40例结直肠癌患者血清和18例健康志愿者血清中验证...目的:探讨血清微小RNA(microRNA,miRNA)在结直肠癌诊断中的价值。方法:通过miRNA表达谱芯片检测7例结直肠癌患者血清和10例健康志愿者血清中差异表达的miRNA。应用实时荧光定量PCR法在40例结直肠癌患者血清和18例健康志愿者血清中验证芯片结果,并分析血清特异性miRNA在结直肠癌诊断中的价值。结果:筛选获得10个在结直肠癌中特异性表达的血清miRNA,实时荧光定量PCR验证后获得一组结直肠癌特异性血清miRNA(miR-129-3p、miR-767-3p及miR-877*)生物标志物,这组生物标志物组合检测结直肠癌的灵敏度为77.78%、特异度为100%,并可产生最大受试者工作特征曲线(receiver operator characteristic curve,ROC)的曲线下面积(area under the curve,AUC)为0.914。结论:miR-129-3p、miR-767-3p和miR-877*生物标志物组合有望成为结直肠癌筛查和早期诊断的指标。展开更多
Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and o...Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.展开更多
文摘目的:低风险微小乳头状甲状腺癌(papillary thyroid carcinoma,PTC)的检出增加与过度诊断和治疗有关。N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)修饰导致的微RNA(microRNAs,miRNA)失调在肿瘤转移和进展中发挥重要作用。然而,m^(6)A靶向miRNAs在PTC中的功能仍不清楚。本研究旨在探究m^(6)A-miR-139-5p在PTC中的表达调控机制,明确其与PTC转移的关联,并评估其作为PTC转移诊断生物标志物的潜力,为PTC的精准诊断和治疗提供实验依据。方法:通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)和GSE130512队列筛选与PTC转移相关的候选靶向m^(6)A-miRNA分子。收集13例PTC转移患者和18例非转移患者的临床标本,检测m^(6)A-miR-139-5p的表达水平,分析其与转移的相关性。通过实验探究脂肪质量和肥胖相关蛋白(fat mass and obesity-associated protein,FTO)对pri-miR-139甲基化水平及加工过程的影响,明确其对miR-139-5p表达的调控作用。在TPC-1细胞中,通过四甲基偶氮唑盐(methyl thiazolyl tetrazolium,MTT)实验检测miR-139-5p过表达对FTO过表达介导的细胞增殖的影响。通过细胞侵袭实验验证miR-139-5p对PTC细胞侵袭能力的作用,并探究其是否通过靶向ZEB1/E-钙黏蛋白轴发挥功能。结果:通过比较TCGA和GSE130512队列,发现血清循环m^(6)A-miR-139-5p可作为检测PTC转移的生物指标。对13例转移和18例非转移临床标本的检测表明,FTO通过降低其甲基化水平抑制pri-miR-139的加工,导致miR-139-5p在PTC中表达失调(P<0.05)。在TPC-1细胞中,MTT实验显示miR-139-5p过表达可部分逆转FTO过表达介导的细胞增殖(P<0.05)。此外,miR-139-5p通过靶向ZEB1/E-钙黏蛋白轴抑制PTC细胞的侵袭能力,而FTO过表达可部分削弱这种抑制效应。结论:血清循环miR-139-5p可作为评估PTC转移的潜在标志物,FTO通过调控pri-miR-139的m^(6)A修饰影响miR-139-5的表达及功能,但其临床价值需进一步验证。
文摘目的探讨急性脑梗死(ACI)患者血清微小RNA-214(miR-214)的表达水平及其临床意义。方法选取2024年1月~2024年2月濮阳市安阳地区医院收治的ACI患者90例设为ACI组,选取同期健康体检者90例为对照组,比较两组血清miR-214水平,使用受试者工作特征(ROC)曲线分析血清miR-214水平对ACI的诊断价值。根据入院24 h美国国立卫生研究院卒中量表(NIHSS)评分将ACI患者分为轻度组(n=44)和中重度组(n=46),比较两组血清miR-214水平和入院24 h NIHSS评分及其相关性。根据发病90 d改良Ranking量表(mRS)评分将ACI患者分为预后良好组(n=40)和预后不良组(n=50),比较两组血清miR-214水平和发病90 d mRS评分及其相关性。比较ACI组和对照组血清炎症因子水平,分析ACI患者血清miR-214表达水平及其与炎症因子水平的相关性。结果ACI组血清miR-214水平低于对照组(P<0.05)。ROC曲线结果显示,血清miR-214对ACI诊断的曲线下面积(AUC)为0.968,最佳截断值为0.71,灵敏度为96.67%,特异度为87.78%。中重度组血清miR-214水平较轻度组更低,NIHSS评分更高(P<0.05);ACI患者血清miR-214水平与NIHSS评分呈负相关性(r=-0.759,P<0.05)。预后不良组血清miR-214水平较预后良好组更低,mRS评分更高(P<0.05);ACI患者血清miR-214水平与mRS评分呈负相关性(r=-0.249,P<0.05)。ACI组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)及中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平均高于对照组(P<0.05);ACI患者血清miR-214表达水平与血清IL-6、TNF-α、CRP及NGAL水平均呈负相关性(P<0.05)。结论ACI患者血清miR-214表达水平异常下降,对ACI具有较高诊断价值,且其与ACI病情严重程度、预后及炎症因子水平均呈负相关性,可能会影响疾病进展。
文摘目的:探讨血清微小RNA(microRNA,miRNA)在结直肠癌诊断中的价值。方法:通过miRNA表达谱芯片检测7例结直肠癌患者血清和10例健康志愿者血清中差异表达的miRNA。应用实时荧光定量PCR法在40例结直肠癌患者血清和18例健康志愿者血清中验证芯片结果,并分析血清特异性miRNA在结直肠癌诊断中的价值。结果:筛选获得10个在结直肠癌中特异性表达的血清miRNA,实时荧光定量PCR验证后获得一组结直肠癌特异性血清miRNA(miR-129-3p、miR-767-3p及miR-877*)生物标志物,这组生物标志物组合检测结直肠癌的灵敏度为77.78%、特异度为100%,并可产生最大受试者工作特征曲线(receiver operator characteristic curve,ROC)的曲线下面积(area under the curve,AUC)为0.914。结论:miR-129-3p、miR-767-3p和miR-877*生物标志物组合有望成为结直肠癌筛查和早期诊断的指标。
基金Acknowledgments We thank Drs Fengyong Liu and Sheng Luan at UC Berkeley, USA, for their discussion and help with the writing of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （no. 30225037, 30471991, 30570731）, National Basic Research Program of China （973 Program） （no. 2006CB503909, 2004CB518603）, the ＂111＂ Project, and the Natural Science Foundation of Jiangsu Province （no. BK2004082, BK2006714）.
文摘Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
