Potential therapeutic targets from genetic and epigenetic approaches for asthma

Asthma is a complex disorder characterised by inflammation of airway and symptoms of wheeze and shortness of breath. Allergic asthma, atopic dermatitis and allergic rhinitis are immunoglobulin E (IgE) related diseases. Current therapies targeting asthma rely on non-specific medication to control airway inflammation and prevent symptoms. Severe asthma remains difficult to treat. Genetic and genomic approaches of asthma and IgE identified many novel loci underling the disease pathophysiology. Recent epigenetic approaches also revealed the insights of DNA methylation and chromatin modification on histones in asthma and IgE. More than 30 microRNAs have been identified to have regulating roles in asthma. Understanding the pathways of the novel genetic loci and epigenetic elements in asthma and IgE will provide new therapeutic means for clinical management of the disease in future.     

抑癌基因RB-蛋白与肿瘤相关的研究进展

RB基因是人类最早发现和确定的抑癌基因,表达产物pRb是重要的细胞周期调节因子,参与细胞的生长分化。pRb功能的缺陷或丧失是很多肿瘤发生的基础,正常RB基因导入恶性肿瘤细胞能全部或部分抑制其恶性表现,也能增加常规化疗和放疗的效果,经截短修饰的RB94在体内和体外都有更好的抑癌作用。但pRb同时也被证实具有保护细胞免于凋亡的作用,此点与其抑癌作用相悖,其各方面功能也可受MicroRNA分子的调控。正是由于RB功能的多面性,近年来对RB与肿瘤的发生、发展和抑制作用的研究从未间断,不断有新的疑问和功能路径被发现。     

MicroRNA in rectal cancer

In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters.     

MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer

MicroRNAs (miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miRNAs in colorectal cancer (CRC) diagnosis. We also shed light on the important corresponding miRNA targets and on the major regulators of miRNAs. Furthermore, we discuss miRNA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miRNAs, the advantages of a therapeutic strategy based on the delivery of miRNA mimics are also mentioned. Together, miRNA seems to be an excellent tool for effectively monitoring and targeting CRC.     

miRNA在间充质干细胞成骨分化过程中的作用

间充质干细胞作为种子细胞在组织工程和再生医学领域有极大的应用前景,尤其是在骨组织工程中的应用受到了广泛关注。间充质干细胞的成骨分化机制复杂,受到多方面因素的影响,不同种类的mi RNA可分别参与抑制或促进间充质干细胞的成骨分化,在其分化过程中具有核心作用。本文对不同作用的mi RNA进行归类和总结,期待为未来的研究提供思路。     

From blood to breath: New horizons for esophageal cancer biomarkers

Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma subtypes. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers.     

重型颅脑损伤病人外周血miRNA生物信息学分析

目的 通过生物信息学方法分析重型颅脑损伤（sTBI）病人外周血微小RNA（miRNA）的靶基因及功能。方法 从GEO数据库中检索获取sTBI病人和对照组外周血的基因芯片数据,应用生物信息学方法筛选差异表达的miRNA,并进行靶基因预测和生物学功能及信号通路分析,构建miRNA及靶基因的调控网络。结果 检索得到芯片GSE21854,筛选得到145个差异表达的miRNA,预测得到靶基因共580个。这些靶基因的功能主要为细胞增殖负性调控、转换生长因子β受体信号通路负性调控等,主要分布在Ras信号通路、转换生长因子β信号通路等。miRNA及靶基因的调控网络图显示hsa-miR-125a-5p、hsa-miR-760、hsa-miR-217、hsa-miR-199a-3p、hsa-miR-543是调控核心。结论 sTBI病人外周血存在差异性表达的miRNA,hsa-miR-125a-5p、hsa-miR-760、hsa-miR-217、hsa-miR-199a-3p、hsa-miR-543与sTBI的进展密切相关。     

血清miR-29联合LncRNA TUG1与ADMA对缺血性脑卒中的鉴别诊断价值

目的 探讨血清微小RNA-29(miR-29)联合长链非编码RNA(lncRNA)TUG1及非对称二甲基精氨酸(ADMA)对缺血性脑卒中的鉴别诊断价值。方法 收集2017年6月-2018年7月本院确诊的缺血性脑卒中患者110例,选取出血性脑卒中患者80例,同期纳入本院的体检健康者100例; 采用实时荧光定量PCR(RT-PCR)法检测血清miR-29和LncRNA TUG1表达水平; 采用酶联免疫吸附法(ELISA)检测血清ADMA水平。结果 与出血性脑卒中组miR-29(60.7±4.3)-log,LncRNA TUG1(16.4±1.4)-log,ADMA(6.3±0.7)mIU/mL和健康对照组miR-29(62.3±4.8)-log; LncRNA TUG1(15.9±1.3)-log; ADMA(6.4±0.6)mIU/mL比较,缺血性脑卒中组血清LncRNA TUG1(43.5±3.5)-log和ADMA(11.4±1.4)mIU/mL水平显著升高,而血清miR-29(31.4±2.1)-log水平显著降低(P<0.05),而出血性脑卒中组和健康对照组血清miR-29、LncRNA TUG1及ADMA水平无明显差异(P>0.05)。Spearman相关性分析显示,血清LncRNA TUG1及ADMA水平与NIHSS评分(LncRNA TUG1:r=0.538,P=0.002; ADMA:r=0.566,P=0.001)呈正相关,而血清miR-29水平与NIHSS评分(miR-29:r=-0.545,P=0.001)呈负相关。血清miR-29、LncRNA TUG1及ADMA区分缺血性脑卒中与非缺血性脑卒中(出血性脑卒中和健康对照者)的AUC分别为0.863(95%CI=0.800～0.944,P<0.001)、0.912(95%CI=0.833～0.977,P<0.001)和0.764(95%CI=0.688～0.887,P<0.001); 敏感度及特异度分别为85.3%/82.1%、94.2%/73.5%和76.8%/81.2%; 对应的临界值分别为48.6-log、33.2-log和9.5 mIU/mL。当联合血清miR-29、LncRNA TUG1及ADMA时区分缺血性脑卒中与非缺血性脑卒中的AUC为0.945(95%CI=0.932～0.998,P<0.001),敏感度为83.8%,特异度为97.3%。结论 联合血清miR-29、LncRNA TUG1及ADMA对缺血性脑卒中具有潜在的鉴别诊断价值。