微小RNA在血管新生和缺血性疾病中的调控作用

血管新生是一种极为重要的生物学过程,微小RNA在血管新生中发挥着重要的调控作用,相关研究已引起广泛关注.文章概述了近年来微小RNA在新生血管形成调控方面的最新研究进展,同时对一些可能参与调控缺血性疾病中血管新生的特异性微小RNA进行了概括.     

microRNA、细胞自噬与肝纤维化

近年来研究发现微小RNA（microRNA）在肝纤维化发生中起到重要调节作用,明晰miR表达谱的差别有助于揭示肝纤维化发生的分子调节机制、发现肝纤维化诊断的分子标志、并有助于发现新的治疗策略。此外研究还发现自噬（autophagy）信号在肝星状细胞（HSC）激活中起到重要作用,静息HSC通过自噬使含维生素A酯的脂滴释放和被利用,以此产生能量来驱动HSC的活化过程。该发现是肝纤维化发生机制的重要补充。     

微小RNA分子miR-214对食管鳞癌细胞Eca109侵袭能力的影响

目的 探讨微小RNA分子miR-214对食管鳞癌细胞Eca109侵袭能力的影响及其可能的分子机制.方法 根据人源miR-214序列合成双链模拟物.通过脂质体转染将miR-214模拟物分子导入食管鳞癌Eca109细胞中,转染无关miRNA模拟物作为对照.采用定量PCR法检测细胞中成熟miR-214分子水平,以Matrigel包被的Transwell实验测定侵袭细胞率,通过蛋白质印迹法检测细胞中E-钙黏蛋白(E-cadherin)的表达,利用流式细胞术检测E-cadherin阳性细胞率.结果 Eca109细胞转染miR-214模拟物48 h后,其成熟miR-214水平较对照组明显上升(P＜0.01);细胞侵袭能力较对照组降低(P＜0.05).同时,miR-214转染组的E-cadherin表达水平及E-cadherin阳性细胞率较对照组下降(P＜0.05).结论 miR-214可能通过抑制细胞上皮间质转化(EMT)的方式抑制食管鳞癌细胞的侵袭能力.     

PR（＋）／PR（-）乳腺癌差异表达microRNAs潜在作用通路的生物信息学分析

目的通过对乳腺癌中与孕激素受体（PR）状态相关的microRNAs差异表达谱进行生物信息学分析,探讨microRNAs在PR表达状态中可能参与的调控机制,为深入研究乳腺癌不同分子亚型的分化提供新思路。方法利用文献挖掘方法找到与PR状态相关的microRNAs差异表达数据集,然后利用生物信息学方法（Targetscan软件和DAVID数据库）预测microRNAs的靶基因,再对靶基因进行基因本体论（GO）富集和通路分析。结果通过文献挖掘找到3个差异表达microRNAs数据集．生物信息学分析获得3个相应靶基因集和1个靶基因合集。靶基因的GO分类主要涉及细胞内的信号级联、蛋白氨基酸磷酸化、蛋白质甲基转移酶活性及转录因子活性等生物学过程及分子功能。通路分析发现3条KEGG信号通路和3条BIOCARTA代谢通路可能参与不同PR表达状态的调节。结论通过生物信息学方法,初步分析了microRNAs在不同PR表达状态中可能参与调控的信号和代谢通路,为进一步探索microRNAs在乳腺癌不同分子亚型分化的调控机制奠定基础。     

MicroRNAs与非可控性炎症相关肿瘤

非可控性炎症与肿瘤之间存在密切的联系,约25%的人类肿瘤是由于非可控性炎症所引起,在几乎所有的肿瘤微环境中存在炎症细胞浸润,炎症细胞及分子影响着肿瘤发生、发展的每一步。MicroRNAs(miRNAs)通过调控一些关键基因及其信号通路,参与了非可控性炎症相关肿瘤起始和进展过程的调控。深入研究miRNAs作用的分子机制,可能为肿瘤的预防、早期诊断及治疗提供新的策略。     

Targeting miR-21 in glioma: a small RNA with big potential

Importance of the field: Glioma therapies have produced relatively small improvements over the past decade, highlighting an important need to identify novel ways to target this disease. Targeted therapies against single activated protein kinases have proven effective in some cancers including gastrointestinal stromal cancer and colon cancer, but not yet in gliomas where multiple pathways and targets may be involved. MicroRNAs are emerging as key regulators of multiple pathways involved in cancer development and progression and may become the next targeted therapies in glioma.

Areas covered in this review: This review covers the basics of microRNA biology and specifically focuses on the roles of miR-21 in glioma and its potential as target for glioma therapy.

What the reader will gain: This review will provide the reader with an in depth understanding of how miR-21 functions in glioma. We also review the current state of studies designed to specifically target miR-21 as a potential future therapeutic.

Take home message: Identifying novel targets for the treatment of glioma is critical for advancing the current state of the field. MicroRNAs provide a novel target; and in glioma, targeting miR-21 may have broad consequences for the tumor that make it an attractive potential therapeutic.     

Stem cell MicroRNAs in senescence and immortalization: novel players in cancer therapy

The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein‐coding RNAs that regulate gene expression. They are involved in important homeostatic processes, such as cellular proliferation, cell death and development, and affect many diseases, including cancer. High‐throughput screenings based on microRNAs related to senescence/immortalization are potential tools for identifying novel proliferative microRNAs that might be involved in carcinogenesis. Recently, a subgroup of highly proliferative microRNAs, which belong to a cluster expressed exclusively in embryonic stem cells and their malignant derivatives (embryonic carcinoma cells), was revealed to play a role in senescence bypass, thereby providing immortalization to human cells. This finding supports the cancer stem cell theory and the relevance of microRNAs in human tumors. This article recapitulates the role of microRNAs that are associated with stem cell properties and their possible link in common pathways related to immortalization and cancer. Ultimately, cancer therapy that is based on the induction of a senescence response is proposed to be highly associated with the loss of stemness properties. Thus, it would be possible to “kill two birds with one stone”: along with the inhibition of stemness properties in cancer stem cells, the senescence response could be induced to destroy the cancer stem cell population within a tumor. © 2011 Wiley Periodicals, Inc. Med Res Rev     

LPS诱发急性肺损伤中miR-16的表达及功能研究

目的 观察脂多糖(LPS)诱发的急性肺损伤中microRNA-16 (miR-16) 的表达变化及其对炎症因子TNF-ɑ等表达的调节.方法 通过生物信息学分析不同物种间miR-16基因序列的保守性.通过小鼠气道向其肺内注入LPS(10 mg·kg-1),构建小鼠急性肺损伤模型,采用实时荧光定量PCR分析miR-16、IL-6、TNF-ɑ的表达水平;在培养的肺上皮细胞A549中采用miR-16 mimic对miR-16进行过表达研究.结果 miR-16基因序列在斑马鱼、大鼠、小鼠和人中序列高度保守;miR-16在急性肺损伤病理过程中表达明显降低(P＜0.05);A549细胞中miR-16的表达水平显著升高(P＜0.01),相反,LPS诱导的炎症因子IL-6、TNF-ɑ的表达水平显著降低(P＜0.05).结论 miR-16在LPS诱发的急性肺损伤病理过程中的表达降低,miR-16过表达能够显著抑制LPS对炎症的诱发作用,表明miR-16在急性肺损伤的炎症发生过程中发挥着重要功能.