患者血清microRNA表达谱及相关生物信息学分析

探讨慢性阻塞性肺疾病（COPD）患者血清中microRNA(miRNA)的差异性表达谱,并通过生物信息学探索其意义。方法 下载GEO数据库开源数据集（GSE70080）,分析慢阻肺患者与正常人血清的miRNA差异性表达谱,分析其对慢阻肺的诊断价值,运用miRTarbase、Target Scan、PicTar 、miRDB等软件预测和筛选miRNAs的靶基因,并将得出的上述靶基因功能富集、信号通路及蛋白质互作网络分析。 结果 该数据集中慢阻肺与健康对照组血清差异表达的miRNA共62个(P＜0.05) ,其中较对照组上调8个,下调54个,上调miRNA和下调miRNA诊断慢阻肺的受试者曲线下面积分别为0.938和0.969。靶基因预测显示差异性表达miRNA共有15099个靶基因,GO功能分析显示上述靶基因主要涉及Wnt、MAPK、NF-κB等重要生物学过程,KEGG分析主要富集于Wnt、NF κB、MAPK等信号通路。miRNA和mRNA的网络图显示SLC4A8与多个miRNA相关。蛋白质互作网络显示靶基因编码蛋白质间存在复杂的相互作用,ACVR1B、ACVRL1、KRT2、KRT74、KRT82在互作网络中具有核心地位。结论 慢阻肺患者的血清miRNA存在差异性表达,miRNA可能通过调控靶基因参与调控相关的生物功能和通路参与慢阻肺发病机制调控     

外泌体微RNA治疗骨关节炎研究进展

骨关节炎是骨科常见的顽固性疾病之一,因其高发病率、高致残率,给患者和社会带来沉重的负担。随着组织工程领域的飞速发展,外泌体治疗骨关节炎的潜力已得到证实。其中,外泌体特异性微RNA（miRNA）可抑制软骨降解和滑膜炎症、促进软骨下骨重塑,从而缓解甚至逆转骨关节炎的病理改变。本文对外泌体miRNA治疗对骨关节炎患者软骨、滑膜、软骨细胞外基质及软骨下骨的影响进行综述,以期为临床上应用外泌体miRNA治疗骨关节炎提供参考。     

Specificity of microRNA target selection in translational repression

MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted miRNA:mRNA interactions must be viewed in the context of other potential interactions and cellular conditions.     

Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life

Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant’s adaptation to enteral nutrition.     

Carbamazepine-induced sperm disorders can be associated with the altered expressions of testicular KCNJ11/miR-let-7a and spermatozoal CFTR/miR-27a

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.     

MicroRNA调控药用植物萜类生物合成研究进展

萜类化合物是药用植物中一类重要的次生代谢产物,对癌症、心血管疾病、疟疾和阿尔茨海默病等多种疾病有效。微RNA（microRNA,miRNA）是一种非编码单链小分子RNA,在转录后水平通过降解目标mRNA或阻断翻译发挥作用。miRNA可以通过作用于萜类生物合成途径的结构基因或转录因子调控药用植物萜类的生物合成。目前,萜类生物合成途径的上游部分研究比较清楚,很多关键酶的编码基因已经被克隆,有的酶分子的空间结构也已被解析,针对参与基因表达调控的转录因子也有一些研究,但对非编码RNA,特别是miRNA参与萜类生物合成的研究较少。对国内外近10年有关miRNA参与萜类生物合成的研究进行综述,以期为高效获取萜类活性成分和阐明萜类药效物质的生物合成提供参考。     

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

微RNA在肿瘤研究中的意义

微RNA（microRNA;miRNA）,又名小分子RNA,是序列特异转录后抑制基因表达的调节因子,是一种长约19～25nt广泛存在于真核细胞胞质内的单链小分子RNA,是一组不编码蛋白质的短序列RNA,它本身不具有开放阅读框（ORF）;成熟的miRNA 5′端有一个磷酸基团,3′端为羟基.miRNA参与生命过程中一系列的重要进程,包括个体发育、造血生成、器官形成、细胞凋亡、细胞增殖与分化、脂肪代谢,甚至肿瘤发生.为更全面地认识miRNA,特别是miRNA在肿瘤诊治中的意义,本文将从以下几个方面对miRNA的研究做一介绍.     

Recently identified drug resistance biomarkers in ovarian cancer

Ovarian cancer, consisting mainly of ovarian carcinoma, is the most lethal gynecologic malignancy. Improvements in outcome for patients with advanced-stage disease are limited by intrinsic and acquired chemoresistance and by tumor heterogeneity at different anatomic sites and along disease progression. Molecules and cellular pathways mediating chemoresistance appear to be different for the different histological types of ovarian carcinoma, with most recent research focusing on serous and clear cell carcinoma. This review discusses recent data implicating various biomarkers in chemoresistance in this cancer, with focus on studies in which clinical specimens have been central.