血清miR-210与新生儿呼吸窘迫综合征严重程度和预后的关系

目的 探讨血清微小RNA-210（mircoRNA-210，miR-210）与新生儿呼吸窘迫综合征（neonatalrespiratory distress syndrome，NRDS）严重程度和预后的关系。 方法 收集NRDS患儿104例，根据预后分为生存组与死亡组。所有新生儿根据首次胸部X线片结果与病情严重程度分为轻度组（Ⅰ级、Ⅱ级）与重度组（Ⅲ级、Ⅳ级）。比较死亡组与生存组患儿一般资料，轻度组与重度组血清miR-210水平与新生儿急性生理学评分围生期补充Ⅱ（perinatal supplement of acute physiological score for neonates Ⅱ，SNAPPE-Ⅱ）评分。绘制ROC曲线分析血清miR-210水平对NRDS患儿死亡的预测价值。采用Spearman相关性分析NRDS发生与血清miR-210的相关性。 结果 根据预后分组，104例患儿中预后较好81例（77.88%），死亡23例（22.12%）。生存组miR-210水平、SNAPPE-Ⅱ评分低于死亡组（P＜0.05）；2组性别、胎龄、出生体重、母亲年龄、病因、剖宫产、双胎、羊水异常差异无统计学意义（P＞0.05）。按照胸部X线片表现分组，104例患儿轻度患儿73例，重度患儿31例。轻度组miR-210水平、SNAPPE-Ⅱ评分低于重度组（P＜0.05）。NRDS发生与血清miR-210水平呈正相关（r=0.638，P＜0.001）。血清miR-210与SNAPPE-Ⅱ评分呈正相关（r=0.513，P＜0.05）。血清miR-210的最佳分界值为16.71 ng/L时，曲线下面积为0.763，OR=0.846，95%CI：0.892~1.064，敏感度为82.61%，特异度为86.42%。结论 血清miR-210水平升高与NRDS病情严重程度以及预后密切相关，血清miR-210水平与NRDS病情程度呈正相关性，当血清miR-210临界值为16.71 ng/L时对评估NRDS患儿预后具有较高价值。     

Post-viral atopic airway disease: pathogenesis and potential avenues for intervention

Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.

Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.

Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.     

miRNA调控实体肿瘤发生发展机制研究进展

microRNA（miRNA）是广泛存在于动物、植物、微生物体内，在转录后水平调控mRNA翻译和降解的内源性染色体编码的小分子RNA。研究证实miRNA对实体肿瘤细胞的发生、增殖、分化、侵袭及转移均具有重要意义。目前miRNA与肿瘤相关性的研究主要集中在检测实体肿瘤组织或体液中miRNA的表达量，明确其对于肿瘤发生、发展的意义；寻找具有临床意义的miRNA靶点，并通过调控其表达抑制肿瘤增殖与转移。miRNA检测方法的进步，也为临床检测miRNA提供了可能。本文对miRNA在实体肿瘤发生发展的作用及其调控机制、以及未来研究方向作综述。     

MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma

MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP‐SAS) was carried out using the miRCURY LNA microRNA Knockdown Library – Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR‐361‐3p (LNA‐miR‐361‐3p) which showed the largest degree of growth inhibition of GFP‐SAS cells. Transfection with a synthetic mimic of mature miR‐361‐3p resulted in an approximately 20% increase in the growth of GFP‐SAS cells. We identified odd‐skipped related 2 (OSR2) as a miR‐361‐3p target gene. Transfection of GFP‐SAS cells with LNA‐miR‐361‐3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3′‐UTR luciferase reporter plasmid and LNA‐miR‐361‐3p into GFP‐SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA‐nontarget. We assessed the effect of LNA‐miR‐361‐3p on the in vivo growth of GFP‐SAS cells. We found that LNA‐miR‐361‐3p significantly reduced the size of s.c. xenografted GFP‐SAS tumors, compared to the control group treated with LNA‐NT. Finally, we observed that miR‐361‐3p is overexpressed in OSCC tissues. These results suggest that miR‐361‐3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR‐361‐3p could be a useful therapeutic approach for patients with OSCC.     

乳腺癌相关microRNA的研究进展

乳腺癌作为一种复杂的、表型多样性的遗传性疾病，涉及基因表达和各种结构的变化。如何早期诊断乳腺癌，降低乳腺癌发病率、死亡率一直是大众关注的焦点。微小RNA（microRNA）是一类内源性非编码单链RNA，广泛参与乳腺癌细胞的增殖、分化、凋亡等生理过程，并与乳腺癌患者的临床分期、淋巴结转移、远处转移等相关。现就microRNA在乳腺癌发生、发展过程中的作用，及其在该病诊疗过程中的应用作一综述，以期为乳腺癌的进一步研究提供新的思路。     

肝癌增强子-miRNA调控作用对的识别与特征分析

目的：探讨肝癌和正常肝组织中增强子与miRNA形成的调控关系及调控miRNA的增强子的特征，筛选出由增强子调控的差异表达miRNA并探讨其与肝癌治疗靶点的相关性。方法：基于TCGA与FANTOM5 数据库，对肝癌和正常肝组织中共417 个样本的增强子与miRNA进行共表达与3D基因组分析得到调控关系。通过ENCODE数据库中肝癌与正常肝组织的组蛋白修饰与转录因子的ChIP-seq 数据分析调控miRNA的增强子上信号值的差异。筛选由增强子调控的差异表达的miRNA，并对患者的生存期与治疗靶点进行相关性分析。结果：在肝癌与正常肝组织中分别识别增强子-miRNA 作用对93 对和40 对。ChIP-seq 数据比对分析发现，肝癌中组蛋白修饰H3K27ac、H3K4me1 和H3K4me3 信号在调控miRNA增强子区域显著高于不调控miRNA的增强子区域（|rho|>0.3，P<0.05）；多种转录因子在肝癌相关增强子中的富集显著低于正常肝组织（|rho|>0.3，P<0.05）。对增强子调控的miRNA进行差异表达分析，识别了6个与肝癌患者生存相关miRNA（hsa-miR-4664、hsa-miR-5003、hsa-miR-1915、hsa-miR-3619、hsa-miR-4745、hsa-miR-6728），发现这些miRNA 与87 个用于靶向治疗的基因以及8 个免疫检查点基因显著相关（|rho|>0.1，FDR<0.05）。结论：成功在肝癌中识别出增强子-miRNA调控作用对与调控miRNA的增强子的特征，并筛选出由增强子调控的与肝癌患者生存和治疗靶点相关的miRNA，为后续深入开展肝癌的基础与临床研究提供了参考依据。     

miRNA失控表达在乳腺癌耐药中研究进展

近年来，乳腺癌耐药的研究取得了显著的进步。microRNA ( miRNA)作为乳腺癌耐药相关的分子标志物及治疗靶点，可能通过药物转运、DNA修复、细胞凋亡、上皮间质转化、乳腺癌干细胞等方面调控乳腺癌耐药。靶向调节miRNA的异常表达，恢复miRNA正常的调控功能，可能为治疗乳腺癌的提供新方向。