血清miR-124 miR-145检测对急性缺血性脑卒中的诊断价值

目的探讨血清microRNA-124(miR-124)、miR-145检测对急性缺血性脑卒中(AIS)的诊断价值及与颈动脉粥样硬化(CAS)斑块性质的关联性。方法选取新乡市第一人民医院收治的AIS患者82例为AIS组,同期健康体检者82例为对照组。对比2组血清miR-124、miR-145水平及与神经缺损程度的关系,探究AIS发病影响因素及各血清的诊断价值,并检测不同CAS斑块性质患者血清miR-124、miR-145水平,分析二者关联性。结果AIS组血清miR-124水平低于对照组,miR-145水平高于对照组(P<0.05);重度患者血清miR-124水平低于中度、轻度患者,血清miR-145水平高于中度、轻度患者(P<0.05);血清miR-124、miR-145为AIS发病的重要影响因素(P<0.05);血清miR-145诊断AIS的AUC(0.791)>miR-124(0.717);易损斑块患者血清miR-124低于稳定斑块患者,血清miR-145水平高于稳定斑块患者(P<0.05);血清miR-124水平与神经功能缺损程度、CAS斑块性质呈负相关,血清miR-145水平与神经功能缺损程度、CAS斑块性质呈显著正相关(P<0.05)。结论血清miR-124、miR-145作为诊断AIS的潜在特异性生物标志物,与神经功能缺损程度、CAS斑块性质存在一定相关性,在AIS患者治疗过程中可通过调节血清miR-124、miR-145表达,发挥保护神经功能、抑制CAS斑块病变进展的作用。     

急性脑梗死患者循环miR-124表达水平与脑梗死体积、神经功能缺损程度的关系及其诊断价值

目的 观察急性脑梗死(ACI)患者循环miR-124表达水平的变化及其与脑梗死体积和神经功能缺损程度的关系和其诊断价值。方法 选择ACI患者90例为观察组,另选取同期体检健康者40例作为对照组; 按梗死体积将ACI患者分为3个亚组:小梗死组(<5 cm³,n=38),中梗死组(5～10 cm³,n=31),大梗死组(>10 cm³,n=21); 根据美国国立卫生研究院卒中量表(NIHSS)评分,将ACI患者分为3个亚组:轻度组(≤6分,n=30)、中度组(7～14分,n=34)、重度组(≥15分,n=26)。通过定量逆转录聚合酶链反应(qRT-PCR)检测循环miR-124相对表达水平; 分析miR-124表达水平与脑梗死体积、神经功能缺损严重程度的关系。结果 观察组miR-124相对表达水平(2.93±1.21)明显高于对照组(1.09±0.55)(t=10.198,P<0.01); 不同脑梗死体积3个亚组间miR-124相对表达水平比较有明显差异(F=20.963,P<0.01),即脑梗死体积越大,miR-124相对表达水平越低; 相关性分析显示,miR-124相对表达水平与梗死体积呈负相关(r=-0.564,P<0.01); 不同NIHSS评分3个亚组间miR-124相对表达水平比较无明显差异(F=1.170,P>0.05)。结论 ACI患者循环miR-124水平明显升高,且其水平与脑梗死体积密切相关。     

不同严重程度阿尔茨海默病患者血清miR-128,miR-223表达水平变化与炎症反应及认知功能的相关性分析

目的 探讨不同严重程度阿尔茨海默病(Alzheimer’s disease,AD)患者血清微小RNA(MicroRNA,miR)-128,miR-223表达水平变化与炎症反应及认知功能的相关性。方法 选择2018年6月-2020年1月本院收治的200例AD患者(AD组),根据临床痴呆评定量表(Clinical dementia rating scale,CDR)评分将AD患者分为轻度组(CDR评分1分,66例)、中度组(CDR评分2分,83例)、重度组(CDR评分3,51例)3个亚组,另选择207例体检健康志愿者为对照组; 采用简易智能精神状态检查量表(Mini-mental state examination,MMSE)评估AD患者认知功能; 检测所有受试者血清miR-128,miR-223表达水平; 检测AD患者血清白介素-6(Interleukin-6,IL-6)、白介素-1β(Interleukin-1,IL-1β)、肿瘤坏死因子-α(Tumor necrosis factor-,TNF-α)、C反应蛋白(C-reactive protein,CRP)水平; 分析血清miR-128,miR-223表达水平与TNF-α,IL-1β,IL-6,CRP水平、MMSE总分的相关性。结果 AD组血清miR-128表达水平高于对照组(P<0.05),miR-223表达水平低于对照组(P<0.05)。重度组血清miR-128表达水平、TNF-α,IL-1β,IL-6,CRP水平高于中度和轻度组(P<0.05),且中度组高于轻度组(P<0.05); 重度组血清miR-223表达水平、MMSE总分低于中度和轻度组(P<0.05),且中度组低于轻度组(P<0.05)。miR-128表达水平与TNF-α,IL-1β,IL-6,CRP呈正相关(r≥0.496,P<0.05),与MMSE总分呈负相关(r =-0.571,P<0.05); miR-223表达水平与TNF-α,IL-1β,IL-6,CRP呈负相关(r ≤-0.572,P<0.05),与MMSE总分呈正相关(r=0.531,P<0.05)。结论 AD患者血清miR-128表达水平上调,miR-223表达水平下调,两者异常变化可能诱导炎症反应,进而参与AD患者认知功能损伤过程。     

血清miR-17-5p与Hcy水平联合预测急性缺血性脑卒中患者预后的价值

目的探讨血清miR-17-5p及同型半胱氨酸(Hcy)水平联合预测急性缺血性脑卒中(AIS)患者预后的价值。方法选取2016年1月至2019年3月儋州市人民医院收治的158例AIS,根据改良Rankin量表(mRS)评分将患者分为预后良好组(n=98,mRS评分≤2分)和预后不良组(n=60,mRS评分2分),采用美国国立卫生研究院卒中量表(NIHSS)评分将患者分为轻度组(n=47,NIHSS评分5分)、中度组(n=73,5分≤NIHSS评分≤20分)、重度组(n=38,NIHSS评分20分)。检测各组血清miR-17-5p及Hcy水平,应用ROC曲线分析miR-17-5p联合Hcy预测AIS患者预后不良的价值。采用Pearson相关分析方法分析AIS患者血清miR-17-5p及Hcy水平与NIHSS及mRS评分的相关性。结果 AIS组血清miR-17-5p[(2.38±0.74)比(0.24±0.08)]及Hcy[(18.60±5.30)μmol/L比(5.70±1.15)μmol/L]水平明显高于对照组(均P0.01)。预后不良组血清miR-17-5p[(3.24±1.08)比(1.56±0.63)]及Hcy[(23.40±6.10)μmol/L比(14.25±3.58)μmol/L]水平明显高于预后良好组(均P0.01)。重度组血清miR-17-5p[分别为:(3.60±1.15)比(2.52±0.90),(3.60±1.15)比(1.20±0.47)]及Hcy[(28.20±6.74)μmol/L比(18.36±4.82)μmol/L,(28.20±6.74)μmol/L比(11.35±3.20)μmol/L]水平均明显高于中度组和轻度组(P0.01),且中度组血清miR-17-5p[(2.52±0.90)比(1.20±0.47)]及Hcy[(18.36±4.82)μmol/L比(11.35±3.20)μmol/L]水平均明显高于轻度组(P0.01)。ROC曲线分析显示,血清miR-17-5p及Hcy水平预测AIS患者预后不良的最佳截值分别为2.06、17.62μmol/L,两项联合预测AIS患者预后不良的曲线下面积[0.918(95%CI:0.860～0.975)]较高,其敏感度和特异度分别为92.0%和85.3%。相关分析结果显示,预后不良组血清miR-17-5p及Hcy水平与NIHSS(分别r=0.772、0.853,P0.01)及mRS评分(分别r=0.740、0.807,P0.01)均呈正相关。结论血清miR-17-5p及Hcy水平升高与AIS患者神经功能缺损的严重程度及预后不良相关,且miR-17-5p联合Hcy对AIS患者预后预测具有较高的价值。     

首发精神分裂症患者外周血miR-22-3p、 miR-92a-3p表达及其对预后的影响

目的:探讨首发精神分裂症患者外周血微小RNA(miR)-22-3p、miR-92a-3p表达及其对预后的影响。方法:给予65例首发精神分裂症患者(患者组)第二代抗精神病药治疗;治疗前采用实时荧光定量逆转录聚合酶链反应(RT-qPCR)技术检测外周血单核细胞中miR-22-3p、miR-92a-3p表达,并与25名健康体检者(对照组)比较;治疗前及1年后随访时分别给予阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)、社会功能缺陷筛选量表(SDSS)评估以及病中攻击行为评定;分析患者miR-22-3p、miR-92a-3p表达与临床相关因素的关系。结果:患者组miR-22-3p、miR-92a-3p相对表达量明显高于对照组;患者组中,miR-22-3p、miR-92a-3p高表达亚组的病程、病中攻击行为比例明显高于低表达亚组(P均0. 05); miR-22-3p、miR-92a-3p高表达亚组1年后随访时PANSS、CGI、SDSS评分显著高于低表达亚组(P均0. 05);多因素Logistic回归分析显示miR-22-3p、miR-92a-3p是影响首发精神分裂症患者预后的危险因素。结论:首发精神分裂症患者外周血miR-22-3p、miR-92a-3p异常高表达,可能是影响患者病情及预后的危险因素。     

首发精神分裂症患者的血清同型半胱氨酸水平及其与P_(300)的关系

目的研究首发精神分裂症患者血清同型半胱氨酸(Homocysteine,Hcy)与事件相关电位P300和临床症状之间的关系。方法采用丹麦KeyPointV2.12脑电生理仪对42例首发精神分裂症患者及28名正常对照进行P300测查,高效液相色谱法测定血清同型半胱氨酸浓度,阳性和阴性症状量表(PANSS)评定患者的临床症状。结果患者组血清Hcy水平高于正常对照组,差异有统计学意义(P0.01)。与对照组比较,患者组P300波幅在Fz点降低(P0.01)。相关分析显示,患者组血清Hcy水平与Fz点的P300波幅呈负相关(r=-0.37,P0.05),而与Pz点的P300潜伏期呈正相关(r=0.34,P0.05);患者组血清Hcy水平与PANSS阴性症状分呈正相关(r=0.49,P0.01);患者组PANSS阴性症状分与Fz点的P300波幅呈负相关(r=-0.39,P0.05)。结论首发精神分裂症患者血清Hcy水平升高,Hcy代谢失衡与精神分裂症的认知功能损害有关。     

首发未治疗精神分裂症血清脑源性神经营养因子水平研究

目的探讨首发未治疗精神分裂症患者血清脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平的变化,及其与精神病未治期(duration of untreated psychosis, DUP)的关系。方法纳入首发未治疗且DUP≤2年的精神分裂症患者93例和正常对照93名。采用阳性和阴性症状量表(positive and negative symptoms scale,PANSS)评定患者的临床症状,并对所有受试者采用酶联免疫吸附法测定血清BDNF浓度。结果精神分裂症组患者血清BDNF水平(10.33±4.68)ng/mL,低于对照组(13.30±5.74)ng/mL,且差异有统计学意义(t=2.191,P=0.033)。患者DUP与其血清BDNF水平无相关性(r=-0.070,P=0.570)。结论首发未治疗精神分裂症患者的血清BDNF水平明显降低;而未治期与血清BDNF水平之间可能没有关联。     

老年急性缺血性脑卒中患者血清miR-150-5p及miR-148b-3p的表达及其临床意义

目的探讨老年急性缺血性脑卒中(AIS)患者血清miR-150-5p及miR-148b-3p的表达水平及其临床意义。方法选取本院收治的178例老年AIS,按照美国国立卫生研究院卒中量表(NIHSS)评分分为:轻度组(52例,NIHSS评分5分)、中度组(83例,5分≤NIHSS评分≤20分),重度组(43例,NIHSS评分 20分)。另选择65例健康体检正常者作为对照组。采用实时荧光定量PCR检测各组血清miR-150-5p及miR-148b-3p表达水平。应用ROC曲线分析血清miR-150-5 p及miR-148 b-3 p表达水平对老年AIS诊断的价值。采用多因素logistic回归分析影响老年AIS的危险因素。结果 AIS组血清miR-125b-5p及miR-148b-3p水平明显低于对照组(P 0. 01)。重度组血清miR-125b-5p及miR-148 b-3 p水平均明显低于中度组和轻度组(P 0. 01)。血清miR-150-5 p及miR-148 b-3 p表达水平诊断老年AIS的最佳临界值分别为2. 82、1. 46,两项联合诊断老年AIS的AUC (95%CI)为0. 927 (0. 868～0. 991),其敏感度和特异度为93. 0%和86. 5%。多因素logistic回归分析显示,miR-150-5 p (OR=3. 107,95%CI:2. 194～6. 715)及miR-148 b-3 p (OR=2. 602,95%CI:1. 713～4. 350)低表达是老年AIS发生的独立危险因素。结论血清miR-150-5 p及miR-148 b-3 p表达水平在老年AIS患者中明显降低,是老年AIS发生的独立危险因素,有望作为老年AIS诊断的生物学标志物。     

帕金森病患者血清微小RNA-128、221的表达水平变化及其临床意义

目的 探讨帕金森病(Parkinson’s disease,PD)患者血清微小RNA(miR)-128,miR-221的表达水平变化及其对疾病的辅助诊断价值。方法 选取2016年1月-2019年12月本院收治的PD患者210例作为PD组,均根据Hoehn-Yahr分级进行分组,4～5期的患者纳入到重度组(60例),2.5～3期的患者纳入到中度组(82例),1～2期患者纳入到轻度组(68例); 收集同期本院的体检志愿者60例作为对照组; 检测所有研究对象的血清miR-128,miR-221表达水平,收集患者的病程以及统一帕金森病评定量表(Unied parkinson disease rating scale,UPDRS)评分。结果 PD组血清miR-128水平低于对照组,血清miR-221水平高于对照组(P<0.05); 重度组血清miR-128水平低于中度组和轻度组,血清miR-221水平高于中度组和轻度组(P<0.05),中度组血清miR-128水平低于轻度组,血清miR-221水平高于轻度组(P<0.05); 经Pearson分析显示,PD患者血清miR-128水平与UPDRS II评分、UPDRS III评分、Hoehn-Yahr分级均呈负相关(-0.5<r<0,P<0.05),血清miR-221水平与UPDRS II评分、UPDRS III评分、Hoehn-Yahr分级均呈正相关(0<r<0.5,P<0.05); 受试者操作特征曲线(Receiver operating characteristic curves,ROC)分析显示,血清miR-128,miR-221对PD有较高的早期辅助诊断价值,其曲线下面积均大于0.7; 联合诊断的敏感度和约登指数均有所提升,联合诊断对PD的早期辅助诊断价值更高。结论 PD患者血清miR-128水平呈异常低表达、miR-221水平呈异常高表达,二者均与患者的病情严重程度存在一定的相关性,且对PD有较高的早期辅助诊断价值。     

急性缺血性脑卒中患者血清miR-103,miR-29b的表达水平变化及其临床意义

目的 探讨急性缺血性脑卒中(AIS)患者血清miR-103,miR-29b的表达水平变化及其临床意义。方法 收集2016年1月-2019年12月本院神经内科收治的126例AIS患者(AIS组),根据美国国立卫生研究院卒中量表(NIHSS)评分将其分为轻度组(45例)、中度组(57例)和重度组(24例),根据改良Rankin量表(mRS)评分将其分为预后良好组(78例)和预后不良组(48例),另选择56例同期于本院门诊体检健康者为对照组,检测血清miR-103,miR-29b表达水平,Spearman秩相关性分析miR-103,miR-29b表达水平与NIHSS,mRS评分的相关性,受试者工作特征曲线(ROC)分析miR-103,miR-29b表达水平对神经功能预后的预测价值。结果 AIS组血清miR-103表达水平高于对照组(P<0.05),miR-29b表达水平低于对照组(P<0.05),血清miR-103表达水平随着AIS患者神经缺损程度加重而升高(P<0.05),miR-29b表达水平则降低(P<0.05)。预后不良组血清miR-103表达水平高于预后良好组(P<0.05),miR-29b表达水平低于预后良好组(P<0.05)。Spearman秩相关性分析显示AIS患者血清miR-103表达水平与NIHSS评分、mRS评分呈正相关(r₂=0.636、0.794,P<0.05),miR-29b表达水平与NIHSS评分、mRS评分呈负相关(r₂=-0.664、-0.659,P<0.05)。ROC分析显示miR-103,miR-29b表达水平预测AIS患者神经功能预后的曲线下面积(AUC)为0.713、0.741,联合miR-103,miR-29b表达水平预测AIS患者神经功能预后的AUC为0.918,高于单独miR-103,miR-29b表达水平(P<0.05)。结论 AIS患者血清miR-103表达水平升高,miR-29b表达水平降低,miR-103表达上调、miR-29b表达缺失均与AIS患者神经功能缺损程度和神经功能恶化有关,可以为患者神经功能预后评估提供参考。     

Association of miR-122, miR-124 miR-126 and miR-143 gene polymorphisms with ischemic stroke in the northern Chinese Han population

Abstract

Objectives: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes can have diverse functional consequence by affecting the processing and target selection of miRNA. Recent evidence indicates that miRNA play important roles in the pathogenesis of atherosclerosis, which is a major cause of ischemic stroke (IS). The aim of this study was to clarify whether genetic variations in four miRNA genes (miR-143 rs4705342, miR-122 rs17669, miR-126 rs4636297, and miR-124 rs531564) contribute to IS susceptibility.

Methods: A case-control study was used to explore miRNA genetic polymorphisms in 567 IS patients and 552 control subjects that were frequency matched by age and gender. We genotyped four SNPs using polymerase chain reaction/ligation detection reaction.

Results: The miR-126 gene rs4636297 polymorphism was associated with decreased small vessel stroke risk (GA vs. GG: odds ratio (OR)?=?0.62, p?=?.015; GA?+?AA vs. GG: OR?=?0.637, p?=?.018; A vs. G: OR?=?0.696, p?=?.033). Using logistic regression analysis, this significant association remained after adjusting for confounding risk factors (adjusted OR?=?0.626, 95% confidence interval (CI)?=?0.426–0.921). However, the three other miRNA (miR-143 rs4705342, miR-122 rs17669, and miR-124 r531564) were not associated with IS risk under allele or genotype, nor in different inheritance models. In addition, there were no significant associations with stroke subtypes for these three miRNA SNPs.

Conclusion: Our study suggests that the miR-126 gene rs4636297 polymorphism may play an important role in the pathogenesis of small vessel occlusive stroke in the northern Chinese Han population.     

Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis

Background

Cerebral atherosclerosis is the most important mechanism for ischemic stroke. However, specific plasma biomarkers to assess atherosclerosis susceptibility are still lacking. Circulating miRNAs have been shown to be promising biomarkers for various pathologic conditions. We investigated whether plasma miR-126 and miR-143 could be used as biomarkers for identifying and evaluating cerebral atherosclerosis. Results showed that miR-143 and miR-126 might participate in the process of atherosclerosis and were minimally affected by cerebral infarction. Using Pearson correlation analysis, we showed that miR-126 and miR-143 were correlated with the presence and severity of cerebral atherosclerosis. The ability of miR-126 and miR-143 to differentiate atherosclerosis patients from healthy controls was demonstrated via a receiving operating characteristic curve with high specificity and sensitivity. Our data thus indicate that miR-126 and miR-143 may be potential specific biomarkers for atherosclerosis.     

miR-181a和miR-181b抑制胶质瘤细胞的增殖和侵袭

目的 探讨miR-181a和miR-181b对胶质瘤细胞增殖和侵袭等影响.方法 通过实时荧光定量PCR检测miR-181a和miR-181b在胶质瘤组织和细胞株中的表达情况.我们合成miR-181a和miR-181b寡聚核苷酸及构建pre-miR-181a和pre-miR-181b表达载体,转染胶质瘤细胞,通过MTT、Transwell实验、流式检测和软琼脂实验,观察上调miR-181a和miR-181b表达后对胶质瘤细胞增殖、侵袭、转化能力和细胞凋亡的影响.结果 miR-181a和miR-181b在胶质瘤组织和细胞株较正常脑组织均呈过低表达;miR-181a表达水平与胶质瘤等级呈负相关.上调miR-181a和miR-181b表达能有效抑制胶质瘤细胞生长,降低其转化和侵袭能力,诱导凋亡.结论 胶质瘤中异常低表达的miR-181a和miR-181b可能发挥着肿瘤抑制因子作用.     

microRNAs miR-124, let-7d and miR-181a regulate Cocaine-induced Plasticity

MicroRNAs play key regulatory roles in cellular processes including neurogenesis, synapse development and plasticity in the brain. Psychostimulants induces strong neuroadaptive changes through a surfeit of gene regulatory mechanisms leading to addiction. MicroRNA profiling for identifying miRNAs regulating cocaine-induced, plasticity-related genes revealed significant regulation of a set of miRNAs upon cocaine administration, especially let-7d, miR-181a and the brain-specific miR-124. These miRNAs target many genes involved in cocaine addiction. Precursor and mature miRNA quantification by qRT-PCR showed that miR-124 and let-7d are significantly downregulated, whereas miR-181a is induced in the mesolimbic dopaminergic system under chronic cocaine administration. Results were confirmed by in situ hybridization, Northern blots, FISH analysis and RNase protection assay. Using lentiviral-mediated miRNA expression, we show a significant downregulation of BDNF and D3R both at mRNA and protein levels by miR-124 and let-7d, respectively. Our data suggest that miR-124, let-7d and miR-181a may be involved in a complex feedback loop with cocaine-responsive plasticity genes, highlighting the possibility that some miRNAs are key regulators of the reward circuit and may be implicated in addiction.     

miR-93、miR-191、 miR-499在颅脑损伤患者血清中的表达及其临床意义

目的 探讨miR-93、miR-191、miR-499在创伤性脑损伤患者中的表达情况及其临床意义。方法 采用实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)方法检测本院2010年9月～2015年9月收治的96例创伤性脑损伤患者以及招募的49例健康者中miR-93、miR-191、miR-499的表达水平,分析其与脑损伤的损伤程度、临床疗效以及诊断价值的关系。结果 miR-93、miR-191、miR-499在创伤性脑损伤患者血清中的表达水平明显高于对照组(P<0.05); 轻度,中度和重度三种不同程度脑损伤患者血清中miR-93、miR-191、miR-499水平都显著性上升,差异具有统计学意义(P<0.05); 而且重度脑损伤患者血清中的miRNAs水平最高; 治疗后临床疗效好的患者血清中miR-93,miR-191,miR-499水平显著低于临床疗效差的患者,差异具有统计学意义(P<0.05); miR-93,miR-191,miR-499三种miRNAs ROC曲线下面积(area under the curve,AUC)分别为0.952 0(95%CI,0.906 5～0.997 4; P<0.001),0.874 6(95%CI,0.793 3～0.955 8; P<0.001),0.780 7(95%CI,0.671 9～0.889 5; P<0.001)。 结论 miR-93,miR-191,miR-499 在创伤性脑损伤患者中高表达,可以作为创作性脑损伤患者的预后和损伤程度指标以及诊断靶标。     

miR-221与miR-222通过靶基因TIMP3调控胶质瘤细胞侵袭能力

目的 探讨miR-221和miR-222在胶质瘤细胞侵袭过程中的作用及其机制.方法 采用反义寡核苷酸下调miR-221和miR-222表达,Transwell、Western blot、荧光素酶实验及体内实验分别检测细胞侵袭能力、体内肿瘤生长、相关基因蛋白表达变化及靶基因鉴定.结果 下调miR-221和miR-222表达能明显抑制胶质瘤细胞侵袭能力,同时相关侵袭蛋白MMP2和MMP9表达下降.miRNA靶基因预测软件分析、Western blot、荧光素酶实验证实TIMP3是miR-221和miR-222的靶基因.裸鼠皮下肿瘤模型显示下调miR-221和miR-222表达抑制体内肿瘤生长.免疫组化发现TIMP3表达上调,MMP2和MMP9表达下调.结论 在胶质瘤细胞中,侵袭相关蛋白TIMP3是miR-221和miR-222的一个新靶基因.

Abstract：

Objective To investigate the role and mechanism of miR -221 and miR -222 in glioma cell invasion. Method After reduction of miR -221 and miR -222 by antisense oligonucleotides, cell invasion,invasion related - gene expression and target identification were determined by Transwell assay, Western blot analysis and luciferase reporter assay,respectively. Moreover,the effects of miR -221 and miR -222 on xenograft tumors in nude mice were also observed. Results Down - regulation of miR - 221 and miR - 222 decreased glioma cell invasion in vitro, and inhibited glioma growth in a subcutaneous mouse model. Furthermore,down -regulation of miR -221 and miR - 222 resulted in obvious inactivation of MMP2 and MMP9. Western blot analysis and luciferase reporter assay showed that the reduction of miR - 221 and miR -222 repressed TIMP3 protein expression and TIMP3 mRNA 3'UTR existed the biding sites of miR -221 and 222. Conclusions TIMP3 is a novel target of miR -221 and miR -222 in glioma cell invasion.     

Effects of miR-219/miR-338 on microglia and astrocyte behaviors and astrocyte-oligodendrocyte precursor cell interactions

MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.