Roles of microRNAs in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.     

MicroRNAs from the Planarian Schmidtea mediterranea: a model system for stem cell biology

MicroRNAs (miRNAs) are approximately 22-nt RNA molecules that typically bind to the 3' untranslated regions of target mRNAs and function to either induce mRNA degradation or repress translation. miRNAs have been shown to play important roles in the function of stem cells and cell lineage decisions in a variety of organisms, including humans. Planarians are bilaterally symmetric metazoans that have the unique ability to completely regenerate lost tissues or organs. This regenerative capacity is facilitated by a population of stem cells known as neoblasts. Planarians are therefore an excellent model system for studying many aspects of stem cell biology. Here we report the cloning and initial characterization of 71 miRNAs from the planarian Schmidtea mediterranea. While several of the S. mediterranea miRNAs are members of miRNA families identified in other species, we also identified a number of planarian-specific miRNAs. This work lays the foundation for functional studies aimed at addressing the role of these miRNAs in regeneration, cell lineage decisions, and basic stem cell biology.     

MicroRNAs,intestinal inflammatory and tumor

Colorectal cancer (CRC) is the third most malignant tumor. Inflammatory bowel disease (IBD) can increase the risk of colorectal cancer. And colitis-associated cancer (CAC) is a CRC subtype, representing the inflammation-related colorectal cancer. For the past decades, we have known that ectopic microRNA (miRNA) expression was involved in the pathogenesis of IBD and CRC, playing a pivotal role in the progression of inflammation to colorectal cancer. Thus, this review provides the recent advances in altered human tissue-specific miRNAs that contribute to IBD, CRC and CAC pathogenesis, diagnosis and treatment. Meanwhile, the potential utilization of miRNAs as novel therapeutic targets for the prevention of CRC was also discussed.     

MicroRNAs: Small molecules with a large impact on pre-eclampsia

As critical mediators in biological processes, microRNAs (miRNAs) which are small and endogenous noncoding RNAs have been associated with disease progression, cell proliferation, and development. Pre-eclampsia (PE), a pregnancy-related disorder with no early markers or symptoms is recognized as the main reason for fetal and maternal mortality and morbidity in the initial steps or even during pregnancy, worldwide. Clinical symptoms usually appear in the third trimester of the pregnancy. Although numerous research have unraveled several aspects of placenta development abnormalities associated with abnormal trophoblastic invasion and angiogenesis modification, many questions about the PE pathogenesis remains unanswered. A large number of studies have shown the important role of miRNAs as potential biomarkers in the PE prognosis and diagnosis. Here, the latest investigations about the PE and placental miRNAs expression, as well as, the crucial role of miRNA molecules including miR-210 and miR-155 which are deregulated in patients with PE, will be argued.     

Export of microRNAs and microRNA-protective protein by mammalian cells

The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research activities, but has left many unanswered questions about how this regulation functions and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell–cell communication. We report here that after serum deprivation several human cell lines tested promptly export a substantial amount of miRNAs into the culture medium and the export process is largely energy dependent. The exported miRNAs are found both within and outside of the 16.5 and 120 K centrifugation pellets which contain most of the known cell-derived vesicles, the microvesicles and exosomes. We have identified some candidate proteins involved in this system, and one of these proteins may also play a role in protecting extracellular miRNAs from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that is consistent with the cell–cell communication hypothesis.     

Interleukin-6 trans-signaling in inflammatory bowel disease

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Recent investigations support the important role of an interleukin-6 (IL-6) signaling pathway in the development of IBD. However, the molecular mechanisms of this pathway in the intestine remain incompletely understood. The circulating and intestinal levels of IL-6 as well as soluble IL-6 receptor (sIL-6R) are increased in patients with IBD. It is remarkable that the mucosal T cells of IBD patients are extremely resistant to apoptosis and that a large fraction of these cells express membrane-bound gp130 but not IL-6R. The accumulated evidence strongly supports the hypothesis that the development and perpetuation of IBD relies on the increased formation of IL-6/sIL-6R complexes interacting with membrane-bound gp130 on T cells via trans-signaling. These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling.     

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed.     

MicroRNA调控的分子影像研究进展

MicroRNAs(miRNAs)是一类长度约为22个核苷酸的RNA分子,它们通过与靶标mRNAs完全或不完全互补配对,进而导致靶标mRNA的降解或翻译的抑制.大量研究表明,它们在细胞增殖、分化、凋亡和肿瘤形成等广泛的生物学过程中都起着重要的作用.传统检测miRNAs表达的方法主要包括Northern杂交、实时定量PC...     

微RNA调节肺癌转移的分子机制

微RNA(microRNA,miRNA)是一类长约22 nt的非编码小分子RNA,在转录后水平上通过基因沉默调节靶基因的活性。近年来,miRNA与肿瘤转移关系的研究成为探讨肿瘤转移调控机制的热点。越来越多的研究提示miRNA在肿瘤转移过程中发挥着重要作用。肺癌转移是影响肺癌预后的关键,是一种复杂的多因素、多步骤、多基因参与调控的过程。研究miRNA对肺癌转移的作用有助于我们找到阻断肺癌转移的靶点。本文就miRNA和肺癌转移关系的研究进展作一综述。     

Regulation of cancer metastasis by microRNAs

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that have been found highly conserved among species. MiRNAs are able to negatively regulate gene expression through base pairing of 3’ UTRs of their target genes. Therefore, miRNAs have been shown to play an important role in regulating various cellular activities. Over the past decade, substantial evidences have been obtained to show that miRNAs are aberrantly expressed in human malignancies and could act as “OncomiRs” or “Tumor suppressor miRs”. In recent years, increasing number of studies have demonstrated the involvement of miRNAs in cancer metastasis. Many studies have shown that microRNAs could directly target genes playing a central role in epithelia-mesenchymal-transition (EMT), a cellular transformation process that allows cancer cells to acquire motility and invasiveness. EMT is considered an essential step driving the early phase of cancer metastasis. This review will summarize the recent findings and characterization of miRNAs that are involved in the regulation of EMT, migration, invasion and metastasis of cancer cells. Lastly, we will discuss potential use of miRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets for cancer.     

Environmental chemicals and microRNAs

MicroRNAs (miRNAs) are short single-stranded non-coding molecules that function as negative regulators to silence or suppress gene expression. Aberrant miRNA expression has been implicated in a several cellular processes and pathogenic pathways of a number of diseases. Evidence is rapidly growing that miRNA regulation of gene expression may be affected by environmental chemicals. These environmental exposures include those that have frequently been associated with chronic diseases, such as heavy metals, air pollution, bisphenol A, and cigarette smoking. In this article, we review the published data on miRNAs in relation to the exposure to several environmental chemicals, and discuss the potential mechanisms that may link environmental chemicals to miRNA alterations. We further discuss the challenges in environmental-miRNA research and possible future directions. The accumulating evidence linking miRNAs to environmental chemicals, coupled with the unique regulatory role of miRNAs in gene expression, makes miRNAs potential biomarkers for better understanding the mechanisms of environmental diseases.