MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses

Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-let-7a miRNA in response to Staphylococcus epidermidis Small Colony Variants infection. We also assessed whether the expression levels of inflammatory cytokines associated with the hsa-let-7a are manipulated by the pathogen and the effect of the IFN-γ priming on the expression of hsa-let-7a and the fate of SCVs/WTs in infected macrophages. A striking observation was the downregulation of the let-7a miRNA upon challenge of the THP-1 activated cells with the SCV isolates while no significant changes in expression were noticed after the infection of macrophages with their WT counterparts. Staphylococcus epidermidis WT and SCV strains were found to invade and survive in macrophages. A significant reduction in bacterial load for both phenotypes was observed in macrophages treated with let-7a mimic compared to untreated ones. Survival of WTs was augmented in cells treated with the inhibitor in 4 out of 5 strains as compared to the number of bacteria recovered from non-transfected cells. At the same time, let-7a inhibitor did not influence on the survival of SCVs in macrophages as their number was comparable to number recovered from non-transfected cells. When the ratio of both let-7a cytokine targets was compared, anti-inflammatory IL-10 cytokine was induced by SCVs predominantly, while the macrophage challenge with WTs was characterized by the inflammatory cytokine profile with high IL-6 and low IL-10 production. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines has been expectedly retrieved when macrophages were transfected with let-7a mimic before infection with WT or SCV strains. The results also show that IFN-γ likely regulates the macrophage environment contributing to the inflammatory response and elimination of bacteria from intracellular milieu by augmenting the synthesis of pro-inflammatory cytokines and supressing the anti-inflammatory IL-10. Our work has shown that SCVs have the potential to regulate the let-7a miRNA to balance the pro-inflammatory IL-6 with anti-inflammatory IL-10 and this mechanism is one of the ways in a complex regulatory network adopted by SCVs to promote their survival.     

MicroRNA在甲状腺癌中的研究进展

微小RNAs(MicroRNAs, miRNAs)是一类短的广泛存在于生物体内,可以调控多种病理及生理过程的单链非编码RNA。研究发现其在组织以外的血液、尿液、外泌体等中也存在差异表达。随着检测技术的飞速发展、研究方法的不断改进以及研究人员操作技能的不断提升,miRNA因其稳定的分子结构以及丰富的生物学功能而进入人们的视线,其在炎症发生、免疫调节、氧化应激、纤维化、信息传递、病毒播散及肿瘤恶性进展等生命进程中的差异表达以及具体的调控机制正在不断被发掘及证实,尤其在甲状腺癌的发生、侵袭、转移及耐药中发挥着重要的调控作用,提示其有望成为甲状腺癌精准诊疗及预后评估的新指标。且对于未知功能的miRNAs以及其在不同类型的甲状腺癌中的特异性表达的研究不仅对于甲状腺癌不同病理类型的诊断、鉴别以及治疗具有重要意义,还有助于动态观察甲状腺癌患者的病情演变。而对于不同甲状腺癌类型相关的特异性miRNA在前者进展中具体调控机制有待进一步的研究。本文对miRNA的研究进程、生物学功能以及其在不同类型的甲状腺癌中的近期研究进行汇总,旨在为甲状腺癌的诊治提供参考,丰富甲状腺癌患者的诊疗策略以及进一步提高甲状腺癌...     

变应性鼻炎继发哮喘患者血浆microRNA表达谱的改变

目的应用microRNA表达谱芯片技术,选取临床明确诊断的变应性鼻炎（allergic rhinitis, AR）及变应性鼻炎罹患哮喘(asthma, AS)患者相应血浆,分析变应性鼻炎患者罹患哮喘后血浆microRNA的差异性表达。方法选取AR及AR+AS各3例,使用miRCURY LNATM芯片,筛选出两组患者血浆中差异表达的microRNA并进行聚类分析;最后通过生物信息学分析预测其靶基因。结果与AR组相比较,AR+AS组差异表达的microRNA共有9个,其中表达下调的有4个,表达上调的有5个。靶基因预测显示,以黏附连接、Wnt和MAPK信号传导通路靶基因的差异表达最为显著。结论通过microRNA芯片发现的相关差异性表达的microRNA,有可能成为AR患者罹患AS的易感性生物标志物及临床可能的治疗靶点,但是尚需要进一步靶基因验证及功能学分析。     

miR-204调控眼科疾病的研究进展

微小RNA(miRNA)是一类广泛存在于真核生物体内、长度为20～ 25个核苷酸、具有调控功能的非编码单链RNA,参与机体的各种生命进程,包括细胞的生长、分化、增生、凋亡和自噬.miRNA-204-5p(miR-204-5p)是由位于染色体9q21.12上的TRPM3大内含子6表达.研究发现,miR-204在角膜损伤愈合过程中起着十分重要的作用,亦能够保持静止状态下血-视网膜屏障的稳定,并且在人小梁网细胞中,miR-204与细胞的凋亡、生存能力以及炎症介质的表达有着重要联系.这些研究都表明miR-204在眼部呈多维表达,提示miR-204很可能是不同眼部疾病的关键miRNA.本文从miRNA的生物合成,miR-204与糖尿病性角膜病变、视网膜色素上皮细胞、人小梁网细胞、年龄相关性白内障、糖尿病视网膜病变、视网膜母细胞瘤的关系,以及miR-204与自噬的相关研究等几个方面,就miR-204调控眼科疾病的研究进展进行综述,为探寻眼部难治性疾病的防治方法寻找新的靶点.     

癌相关成纤维细胞外泌体携带微小RNA-20a靶向CX43调控细胞缝隙连接促进PC-3细胞侵袭和迁移

目的:探讨癌相关成纤维细胞(CAFs)来源外泌体微小RNA(miR)-20a对前列腺癌细胞间通讯连接(GJIC)、侵袭和转移能力的影响及其机制。方法:构建CAFs来源近红外荧光蛋白(IRFPs)标记外泌体,以不同浓度(0、10、100、200 mg/L)与PC-3细胞共培养。蛋白质印迹法检测PC-3细胞中CX43蛋白的...     

Regulatory role of microRNAs in cancer through Hippo signaling pathway

Cancer is the major cause of death worldwide in countries of all income levels. The Hippo signaling pathway is a Drosophila kinase gene that was identified to regulate organ size, cell regeneration, and contribute to tumorigenesis. A huge variety of extrinsic and intrinsic signals regulate the Hippo signaling pathway. The Hippo signaling pathway consists of a wide array of components that merge numerous signals such as mechanical signals to address apoptosis resistance, cell proliferation, cellular outputs of growth, cell death and survival at cellular and tissue level. Recent studies have shed new light on the regulatory role of microRNAs in Hippo signaling and how they contribute to cancer progression. MicroRNAs influence various cancer-related processes such as, apoptosis, proliferation, migration, cell cycle and metabolism. Inhibition and overexpression of miRNAs via miRNA mimics and miRNA inhibitors, respectively, can uncover a hopeful and reliable insight for treatment and early diagnosis of cancer patients. In this review we will discuss our current understanding of regulatory role of miRNAs in Hippo signaling pathway.     

微RNA与肺癌治疗的研究进展

微RNA(miRNA)是一种内源性长为18²5个核苷酸的小分子非编码RNA,通过与特定mRNA 3'UTR(非编码区)结合抑制蛋白质表达参与生物的发育、代谢及肿瘤的发生、发展等生命现象。近年来,越来越多的研究显示miRNA几乎在肺肿瘤癌变的每一个过程(如肿瘤的发生、侵袭和转移)以及抗癌药物等方面产生影响,miRNA在肺癌中发挥原癌基因的作用及抑癌基因的作用。因此,miRNA很有可能成为肺癌靶向治疗的有效靶点,为肺癌的治疗提供新方法。该文结合国内外最新报道,论述miRNA在肺癌治疗方面的研究进展。     

MicroRNA在山楂酸诱导A549细胞凋亡中的作用研究

目的探讨MicroRNA在山楂酸诱导肺癌细胞A549凋亡过程中发挥的生物学作用。方法将人的肺癌细胞系A549经过山楂酸干预,并提取处理后A549细胞的总RNA,通过AFFX miRNA表达谱芯片,检测山楂酸作用前后A549细胞中miRNA表达差异情况。通过生物信息学,分析预测miRNA作用的靶蛋白。结果山楂酸作用前后肺癌细胞A549中59个miRNA表达差异显著,其中23个miRNA的表达上调,36个miRNA的表达下调。生物信息学分析预测,由miRNA调控的细胞增殖相关靶蛋白400余个,细胞凋亡相关靶蛋白300余个,其中XIAP是miR-630下游调控的靶蛋白。结论山楂酸可能通过调控miRNA的表达发挥对A549细胞的抑制作用。