lncRNA RP11-86H7.1在川崎病诊断中的临床意义

目的：探讨lncRNA RP11-86H7.1在川崎病（KD）患者血清中的表达及其与临床病理特征及预后的关系。方法：筛选KD特异相关的循环lncRNA,分KD治疗前患儿组、KD治疗后患儿组、普通发热患儿组及健康儿童组,采用qPCR检测各组血清lncRNA RP11-86H7.1相对表达。分析血清lncRNA RP11-86H7.1相对表达与KD临床病理特征间关系;绘制ROC曲线,分析血清lncRNA RP11-86H7.1表达水平对KD的诊断效能。结果：KD急性患儿组血清lncRNA RP11-86H7.1相对表达量高于各对照组（P＜0.05）;年龄和性别比例与低表达组比较差异无统计学意义（P＞0.05）;qPCR发现lncRNA RP11-86H7.1在KD急性期患儿血清中表达水平明显高于KD恢复期、健康儿童及发热儿童组,差异均有统计学意义（P＜0.05）。结论：血清lncRNA RP11-86H7.1在KD患者中表达上调,其可作为KD早期诊断和评估预后的潜在的生物标志物。     

高氧诱导支气管肺发育不良新生小鼠肺组织中lncRNA表达谱的变化

目的:分析长链非编码RNA (long non-coding RNA,lncRNA)在高氧诱导支气管肺发育不良(bronchopulmonary dysplasi,BPD)小鼠模型肺中表达谱的变化?方法:构建高氧诱导支气管肺发育不良新生小鼠模型,利用lncRNA芯片技术检测正常小鼠肺及BPD小鼠肺组织中lncRNA表达谱的变化,经过对原始数据进行预处理,筛选出差异表达的lncRNA?结果:与对照组相比,模型组差异表达的lncRNA(差异倍数≥2倍且P < 0.05)共1 769条,其中882条上调,887条下调;5倍以上上调的共140条,下调的共71条;10倍以上上调的共28条,下调的有2条?结论:高氧诱导BPD发生时,肺组织中lncRNA的表达谱发生了显著变化;这些差异表达的lncRNA,可能参与了BPD发生?发展过程?     

Genetic variants within ANRIL (antisense non coding RNA in the INK4 locus) are associated with risk of psoriasis

BackgroundPsoriasis is a systemic inflammatory disease which mostly affects skin. Evidences support the role of autoimmune responses in this disorder. The long non-coding RNA (lncRNA) antisense non coding RNA in the INK4 locus (ANRIL) has been shown to participate in modulation of immune response and in the pathogenesis of immune-related disorders.MethodsWe genotyped four single nucleotide polymorphisms (SNPs) with this lncRNA (rs1333045, rs1333048, rs4977574 and rs10757278) in 286 patients with psoriasis and 300 age-/sex-matched controls to identify the role of ANRIL as a risk locus for psoriasis.ResultsThe C allele of rs1333048 SNP was significantly more prevalent among cases compared with controls (OR (95% CI) = 1.56 (1.23–1.97), adjusted P value = 8.31E−4). The A allele of the rs4977574 had a protective effect against psoriasis (OR (95% CI) = 0.63 (0.49–0.81), adjusted P value = 0.001). The G allele of the rs10757278 conferred risk of psoriasis in the assessed population (OR (95% CI) = 1.9 (1.51–2.4), adjusted P value = 2.18 E−7). The C A G A haplotype (rs1333045, rs1333048, rs4977574 and rs10757278, respectively) was reported to be a protective haplotype against psoriasis (OR (95% CI) = 0.5 (0.35–0.71), adjusted P value = 0.001). The C A G G and T C G G haplotypes conferred risk of psoriasis in the assessed population (OR (95% CI) = 2.37 (1.59–3.54), adjusted P value = 2.4E−4; OR (95% CI) = 5.42 (2.88–10.22), adjusted P value = 1.1E−7, respectively).ConclusionConsequently, ANRIL can be regarded as a risk locus of psoriasis in the assessed population. Future studies are needed to verify whether this contribution is exerted through modulation of immune responses.     

A potential association of RNF219-AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

AimsAttention‐deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder of substantial heritability, yet emerging evidence suggests that key risk variants might reside in the noncoding regions of the genome. Our study explored the association of lncRNAs (long noncoding RNAs) with ADHD as represented at three different phenotypic levels guided by the Research Domain Criteria (RDoC) framework: (i) ADHD caseness and symptom dimension, (ii) executive functions as functional endophenotype, and (iii) potential genetic influence on white matter architecture as brain structural endophenotype.MethodsGenotype data of 107 tag single nucleotide polymorphisms (SNP) from 10 candidate lncRNAs were analyzed in 1040 children with ADHD and 630 controls of Chinese Han descent. Executive functions including inhibition and set‐shifting were assessed by STROOP and trail making tests, respectively. Imaging genetic analyses were performed in a subgroup of 33 children with ADHD and 55 controls using fractional anisotropy (FA).ResultsOne SNP rs3908461 polymorphism in RNF219‐AS1 was found to be significantly associated with ADHD caseness: with C‐allele detected as the risk genotype in the allelic model (P = 8.607E‐05) and dominant genotypic model (P = 9.628E‐05). Nominal genotypic effects on inhibition (p = 0.020) and set‐shifting (p = 0.046) were detected. While no direct effect on ADHD core symptoms was detected, mediation analysis suggested that SNP rs3908461 potentially exerted an indirect effect through inhibition function [B = 0.21 (SE = 0.12), 95% CI = 0.02‐0.49]. Imaging genetic analyses detected significant associations between rs3908461 genotypes and FA values in corpus callosum, left superior longitudinal fasciculus, left posterior limb of internal capsule, left posterior thalamic radiate (include optic radiation), and the left anterior corona radiate (P _{FWE corrected} < 0.05).ConclusionOur present study examined the potential roles of lncRNA in genetic etiological of ADHD and provided preliminary evidence in support of the potential RNF219‐AS1 involvement in the pathophysiology of ADHD in line with the RDoC framework.     

rhIL23R-CHR/Fc融合蛋白通过下调ENST00000522718抑制Act-HaCaT细胞炎症和增殖

银屑病是一种以慢性皮肤炎症为主要特征的自身免疫性疾病,其病因及发病机制尚未完全阐明。本研究在前期rhIL23R-CHR/Fc融合蛋白显著改善银屑病小鼠症状并初步阐明药理机制的基础上,利用TNF-α刺激人皮肤永生化角质形成细胞株（HaCat）,建立银屑病细胞模型（Act-HaCaT）,通过转录组测序并结合qRT-PCR,筛选rhIL23R-CHR/Fc融合蛋白调控Act-HaCaT细胞功能时发挥关键作用的lncRNA分子。研究结果表明,rhIL23R-CHR/Fc融合蛋白能够显著抑制Act-HaCaT细胞增殖和炎症因子产生,通过筛选得到lncRNA ENST00000522718,并发现敲低ENST00000522718能够显著抑制细胞增殖和炎症因子产生,提示ENST00000522718在银屑病的病理机制中发挥着重要作用。