Association study of miR-146a,miR-149, miR-196a2, and miR-499 polymorphisms with venous thromboembolism in a Korean population

Journal of Thrombosis and Thrombolysis - Despite much progress in microRNA (miRNA) research, information regarding the association between miRNAs and venous thromboembolism (VTE), especially in...     

肺癌细胞及组织中miR-181a、miR-200a、miR-200c表达变化及意义

目的：观察肺癌细胞及组织中 miR-181a、miR-200a、miR-200c 的表达变化,并探讨其临床意义。方法选择人肺癌细胞系NCI-H1299、NCI-H358、H460、A549及人正常支气管上皮细胞HBE,10例肺癌患者的癌组织及其相应癌旁组织。采用RT-PCR法检测各细胞系及组织中的miR-181a、miR-200a、miR-200c,并分析miRNA表达与临床参数的关系。结果 NCI-H1299、NCI-H358、A549细胞中miR-181a相对表达量均低于HBE细胞,NCI-H1299、NCI-H358、H460、A549细胞中miR-200a相对表达量均低于HBE细胞,NCI-H358、H460细胞中miR-200c相对表达量均高于HBE细胞,P均＜0．05。肺癌及癌旁组织中miR-181a和miR-200a相对表达量比较,P均＞0．05;肺癌组织中miR-200c相对表达量高于癌旁组织,P＜0．01。有淋巴结转移的肺癌患者miR-200a相对表达量低于无淋巴结转移者,P＜0．01;其余miRNA相对表达量与临床病理参数均无关,P均＞0．05。结论 miR-181a、miR-200a在肺癌细胞株中表达普遍降低,而miR-200c在肺癌细胞及组织中表达普遍升高,可能与肺癌的发病有关。     

先天性心脏病相关性肺动脉高压患者血miR-18a、miR-27b、miR-130a、miR-204水平研究

目的 探索先天性心性脏病相关性肺动脉高压（PAH）患者血清中miR-18a、miR-27b、miR-130a和miR-204的表达水平,以及与PAH的相关性.方法 收集昆明医科大学附属延安医院心血管内科2012年4～12月被确诊为先天性心脏病的患者78例,其中肺动脉压正常组37例,合并轻、中度肺动脉高压组25例,重度肺动脉高压组16例;另设正常对照组20例.应用实时荧光定量PCR （Taqman探针法）检测miR-18a、miR-27b、miR-130a、miR-204在血液中的表达水平,分析先天性心脏病相关性肺动脉高压与miR-NA表达水平之间的关系.结果 先天性心脏病相关肺动脉高压患者血miR-18a、miR-27b、miR-130a表达水平显著上调,miR-204表达水平显著下调.随着肺动脉压力的不断增高,血miR-18a、miR-27b、miR-130a表达量明显升高,miR-204表达量显著下调.直线相关分析显示,先天性心脏病继发性肺动脉高压患者血miR-18a、miR-27b、miR-130a表达水平与肺动脉压力存在高度正相关关系（r=0.927,r=0.927,r=0.933,P＜0.01）,miR-204表达水平与肺动脉压力存在高度负相关关系（r=-0.773,P＜0.01）.结论 血miR-18a、miR-27b、miR-130a、miR-204水平可作为判断先天性心脏病合并肺动脉高压较好的临床血清学指标,预判价值较高.     

内皮细胞缺氧后miR-210、miR-92a、miR-126表达及意义

目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型（观察组）,正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA（miR-210、miR-92a、miR-126）表达变化。结果与对照组比较,miR-210、miR-92a、miR-126分别上调了（5.19±0.99）、（3.02±0.88）、（3.87±0.83）倍,P均〈0.05。结论缺氧可促使内皮细胞特异性microRNA表达改变,此可能为缺氧后血管新生的主要调控机制。     

Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

AIM: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR-146a genes are associated with sporadic colorectal cancer (CRC).METHODS: In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.RESULTS: The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results.CONCLUSION: Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.     

血清miR-21、miR-148b、miR-200a、miR-200b在原发性肝癌患者中的表达及临床诊断意义

目的研究原发性肝癌(HCC)患者血清中微小RNA(miR)-21、miR-148b、miR-200a、miR-200b的表达及临床诊断意义。方法应用实时荧光定量逆转录-聚合酶链反应(qRT-PCR)检测西南医科大学附属医院收治的93例HCC患者(病例组)、48例肝脏良性病变(良性组)、48例慢性肝病患者(慢性肝病组)和50例健康体检者(对照组)血清中miR-21、miR-148b、miR-200a、miR-200b的表达。统计学分析各指标与临床病理特征之间的关系,受试者工作特征(ROC)曲线分析各指标的诊断价值。结果病例组血清miR-21与miR-200b表达显著高于良性组、慢性肝病组及对照组(均P<0.05),miR-200a与miR-148b表达显著低于良性组、慢性肝病组及对照组(均P<0.05)。HCC患者血清miR-21与miR-200b表达与病理分期、病理分级及肿瘤直径有关(均P<0.05),与性别、年龄、有无肝硬化及乙型肝炎病毒(HBV)抗原是否阳性无关(均P>0.05)。血清miR-200a与miR-148b表达与病理分期、病理分级有关(均P<0.05),与性别、年龄、肿瘤直径、有无肝硬化及HBV抗原是否阳性无关(均P>0.05)。miR-21、miR-148b、miR-200a、miR-200b及四项指标联合的ROC曲线下面积(AUC)分别为0.821、0.668、0.772、0.734、0.922。联合诊断的敏感性和特异性均高于任一单一指标。结论HCC患者血清miR-21与miR-200b表达上调,而miR-200a与miR-148b表达下调。并且其表达与病理分期、病理分级有关,联合检测血清miR-21、miR-148b、miR-200a、miR-200b有希望成为新的诊断HCC的肿瘤标志物。     

结直肠癌患者组织中miR-99a和miR-100表达水平与肿瘤转移的关系

目的 探讨结直肠癌组织中miR-99a、miR-100的表达水平与肿瘤转移的关系.方法 收集2014年1月至2019年1月台州市第一人民医院收治的84例行手术治疗的结直肠癌患者的肿瘤组织、癌旁组织和正常组织标本,采用实时荧光定量PCR法检测各组织中miR-99a、miR-100的表达水平,收集患者的临床病理参数及随访情...     

Association of miR-146 rs2910164,miR-196a rs11614913,miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease

AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven patients with CD based on standardclinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and nonresponders. Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study. Seventy two(67.3%) patients were classified as complete responders, 22(20.5%) as partial while 13(12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to antiTNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.     

体外与非体外循环冠状动脉旁路移植术后血清miR-1、miR-133a、miR-208a水平变化及分析

目的探究行体外循环冠状动脉旁路移植术(ONCABG)与非体外循环冠状动脉旁路移植术(OPCABG)患者术后血清miR-1、miR-133a、miR-208a水平变化。方法选取2016年2月—2019年2月本院多支冠状动脉病变需要行CABG的患者94例。根据手术方式,将94例患者分为ONCABG组47例和OPCABG组47例。利用荧光实时定量PCR法检测所有患者术前、术后不同时间血清miR-1、miR-133a、miR-208a水平。采用化学发光免疫分析仪检测所有患者术前、术后不同时间血清心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)水平。分析血清miR-1、miR-133a、miR-208a水平与cTnI、CK-MB水平的相关性。结果与术前相比,两组患者术后4 h、24 h血清miR-1、miR-133a、miR-208a、cTnI、CK-MB水平升高(P0.05)。与术后4 h相比,两组患者术后24 h血清miR-1、miR-133a、miR-208a、cTnI、CK-MB水平降低(P0.05)。与ONCABG组相比,OPCABG组术后4 h、术后24 h血清miR-1、miR-133a、miR-208a、cTnI、CK-MB水平降低(P0.05)。Pearson分析显示,两组患者术后4 h、术后24 h血清miR-1、miR-133a、miR-208a水平与cTnI、CK-MB水平均呈正相关(P0.05)。结论 miR-1、miR-133a、miR-208a有望作为判断ONCABG与OPCABG后心肌损伤的重要生物标志物。本研究为ONCABG与OPCABG在临床上的选择提供了一定的参考依据。     

MicroRNA-132, miR-146a,and miR-155 as potential biomarkers of methotrexate response in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) patients have high expression levels of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p in peripheral blood. We studied if baseline blood...     

Evaluation of MicroRNAs miR-196a,miR-30a-5P,and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Background and objectives

This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.

Design, setting, participants, & measurements

Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.

Results

All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of ≥0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P<0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P>0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03).

Conclusions

The levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.     

非小细胞肺癌患者血浆miR-10b、miR-122、miR-16和miR-183水平及其与总生存期的关系

目的观察非小细胞肺癌(NSCLC)患者血浆miR-10b、miR-122、miR-16、miR-183水平,并探讨其与患者总生存期(OS)的关系。方法选择NSCLC患者40例,其中术后复发32例、无复发8例。采用实时荧光定量PCR法检测血浆miR-10b、miR-122、miR-16、miR-183。以各miRNA水平均数为界值,将NSCLC患者分为miRNA高水平和低水平,分析不同miRNA水平与患者OS的关系。结果无复发者血浆miR-183水平高于复发者(P<0.05),其余miRNA水平二者比较P均>0.05。miR-183低水平者OS高于高水平者(P<0.05),其余miRNA不同水平者OS比较P均>0.05。Cox比例风险回归模型分析显示,miR-183是NSCLC患者OS的独立影响因素(HR=2.854,95%CI为1.154~7.055,P<0.05)。结论 miR-183可能是NSCLC患者OS的独立影响因素,而miR-10b、miR-122和miR-16与患者OS无关。     

非酒精性脂肪性肝病合并2型糖尿病患者外周血miR-17、miR-20a和miR-20b变化及其临床意义*

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者外周血miR-17、miR-20a和miR-20b变化及其临床意义。方法 2018年12月～2020年6月我院收治的T2DM患者46例和NAFLD合并T2DM患者50例(轻度19例、中度17例和重度14例)。采用实时荧光定量RT-PCR法检测血清miR-17、miR-20a和miR-20b mRNA水平。采用多因素Logistic回归分析NAFLD合并T2DM发生的独立危险因素,应用受试者工作特征曲线(ROC)下面积(AUC)分析各指标诊断严重NAFLD的效能。结果 NAFLD合并T2DM患者外周血miR-17、miR-20a和miR-20b mRNA水平分别为(5.6±1.3)、(3.8±0.9)和(1.8±0.5),显著高于T2DM患者【分别为(4.4±1.1)、(3.1±0.6)和(1.4±0.4),P<0.05】;重度NAFLD组血清miR-17、miR-20a和miR-20b mRNA水平分别为(6.0±1.1)、(4.0±0.8)和(1.9±0.5),显著高于中度患者【分别为(4.4±1.0)、(3.4±0.6)和(1.5±0.4),P<0.05】或轻度患者【分别为(4.1±0.6)、(2.8±0.8)和(1.2±0.3),P<0.05】;多因素Logistic回归分析显示,BMI、血清LDL-C、miR-17、miR-20a和miR-20b是NAFLD合并T2DM发生的独立危险因素(P<0.05);ROC分析结果显示,血清miR-17、miR-20a和miR-20b诊断严重NAFLD的AUC分别为0.75、0.74和0.70。结论 NAFLD合并T2DM患者外周血miR-17、miR-20a和miR-20b水平显著升高,可能参与了NAFLD的发病过程,对判断NAFLD的严重程度具有一定的意义。     

miR-328、miR-147和miR-22在冠心病患者中的表达变化及临床意义

目的探讨冠心病患者血浆及外周血单个核细胞(PBMC)miR-328、miR-22、miR-147的表达变化及其临床意义。方法筛选100例冠心病患者及相对健康对照组,采用实时荧光定量PCR技术检测各组血浆及PBMC中miR-328、miR-147、miR-22的表达水平。结果冠心病患者血浆中miR-328、miR-22的表达较非冠心病患者明显升高,而miR-147的表达明显降低;在冠心病患者PBMC中,miR-328表达没有明显变化,miR-22表达略微增加,miR-147表达明显下降。在心肌梗死患者中,血浆中miR-328和miR-22表达水平明显增加,而miR-147表达明显下降;心肌梗死患者PBMC中miR-328表达略降低,miR-22表达增加,miR-147表达水平略有下降。结论 miR-328、miR-22及miR-147在冠心病患者中的差异表达,有望作为冠心病疾病中一种新的标记物或基因治疗靶点。     

MicroRNAs、uPA及MMP-3在骨关节炎患者滑膜组织中的表达及相关性

目的比较MicroRNAs、uPA及MMP-3在骨关节炎(OA)患者与正常关节滑膜中的表达差异,了解其在OA滑膜病变中的作用。方法采用实时定量PCR技术检测miR-27a、miR-140、uPA和MMP-3在33例OA患者与28例正常关节滑膜中的表达水平,并分析其相关关系。结果 OA组miR-27a、miR-140、uPA和MMP-3相对表达量分别为(1.63±0.93)、(0.94±0.60)、(3.52±1.79)和(4.91±1.86),非OA组miR-27a、miR-140、uPA和MMP-3相对表达量分别为(3.34±1.68)、(2.55±1.12)、(1.16±0.65)和(0.84±0.57),组间比较显示miR-27a、miR-140的表达OA组显著低于对照组(P<0.01),而uPA和MMP-3表达OA组明显高于对照组(P<0.01);OA组内各因子之间相关分析显示,miR-27a和uPA呈显著相关关系,相关系数为r=-0.699(P<0.01),miR-140和MMP-3呈显著相关关系,相关系数为r=-0.598(P<0.01);uPA和MMP-3之间也呈相关关系,相关系数为r=0.444(P<0.05)。结论 miRNA-27a、miRNA-140在OA患者滑膜中低表达,二者与在滑膜中呈现高表达的uPA和MMP-3分别呈现显著负相关关系,共同作用于OA滑膜和软骨退变过程。     

Predictive Value of Serum miR-10b,miR-29c,and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. The high mortality of ESCC is mainly due to late diagnosis. Current detection methods have their own weakness, including high costs and invasive procedures. MicroRNA assays are shown to have great potential to be accurate and noninvasive methods for ESCC screening. In this study, we selected 3 microRNAs, miR-10b, miR-29c, and miR-205, to assess their diagnostic value in ESCC screening. Fifty ESCC patients and 50 healthy controls are recruited in our study. Blood samples are collected from the total 100 participants. MicroRNAs were extracted from serum and quantified by qRT-PCR, which their relative expressions were normalized by internal control, U6 snRNA. Statistical analyses were conducted to compare microRNAs level as well as other clinical characteristics between 2 groups. The levels of serum miR-29c and miR-205 were significantly downregulated in ESCC patients compared with healthy volunteers. In contrast, ESCC patients appeared to have a higher level of miR-10b than healthy controls. ROC curve analyses revealed that the AUC value for miR-10b, miR-29c, and miR-205 were 0.85 (95% CI: 0.79–0.93; sensitivity = 76%; specificity = 84%), 0.72 (95% CI: 0.62–0.82; sensitivity = 68%; specificity = 68%), and 0.72 (95% CI: 0.62–0.83; sensitivity = 70%; specificity = 64%), respectively, suggesting that miR-10b, miR-29c, and miR-205 have great potential to be noninvasive screening tools for ESCC detection.     

Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies

AIM: To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues.METHODS: The relative expression levels of miR-21, miR-33a, miR-96, miR-122, miR-125b, miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C (CHC and CHC-Steatosis, respectively) cases, 18 non-infected, steatotic liver biopsies of metabolic origin (Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays. All CHC biopsy samples were obtained prior to initiating therapy. Patients’ serum biochemical values, which included glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), alkaline phosphatase (AP), were obtained and correlated with relative miRNA expression.RESULTS: When compared with control non-infected liver samples, miR-122 and miR-221 levels were reduced in CHC-Steatosis (P < 0.03) and in CHC, CHC-Steatosis and Steatosis (P < 0.01). Alternatively, the expression of miR-33a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue (P < 0.01). The levels of miR-33a and miR-224 in CHC-Steatosis (P < 0.02) and miR-224 in Steatosis (P < 0.001) were increased in comparison to CHC samples. By contrast, the expression of miR-21 did not differ statistically between diseased and normal liver samples. Levels of miR-33a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC, whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis. In contrast, miRNA levels were not correlated with ALT, GGT, cholesterol levels or fibrosis stage.CONCLUSION: Differences in miRNA expression were observed between CHC and steatotic CHC, CHC and steatotic liver, but not between steatotic CHC and steatotic liver of metabolic origin.