Expression profiles of MicroRNAs from multiple lumbar spine in sheep
Xiangyu ZhangCunyuan LiXiaoyue LiZhijin LiuWei NiWureli HaziYang CaoYang YaoDawei WangXiaoxu HouShengwei Hu
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Understanding how gene expression systems influence biological outcomes is an important goal for diverse areas of research. Gene expression profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to use this information to increase biological understanding. Yet, the best way to relate this immense amount of information to biological outcomes is far from clear. Here, a novel approach to gene expression systems research is presented that focuses on understanding gene expression systems at the level of gene expression program regulation. It is suggested that such an approach has important advantages over current techniques and may provide novel insights into how gene expression systems are regulated to shape biological outcomes such as the development of disease or response to treatment.
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Regulation of gene expression levels is essential for all living systems and transcription factors (TFs) are the main regulators of gene expression through their ability to repress or induce transcription. A balance between synthesis and degradation rates controls gene expression levels. To determine which rate is dominant, we analyzed the correlation between expression levels of a TF and its regulated gene based on a mathematical model. We selected about 280,000 expression patterns of 355 TFs and 647 regulated genes using DNA microarray data from the Gene Expression Omnibus (GEO) data repository. Based on our model, correlation between the expressions of TF-regulated gene pairs corresponds to tuning of the synthesis rate, whereas no correlation indicates excessive synthesis and requires tuning of the degradation rate. The gene expression relationships between TF-regulated gene pairs were classified into four types that correspond to different gene regulatory mechanisms. It was surprising that fewer than 20% of these genes were governed by the familiar regulatory mechanism, i.e., through the synthesis rate. Moreover, we performed pathway analysis and found that each classification type corresponded to distinct gene functions: cellular regulation pathways were dominant in the type with synthesis rate regulation and terms associated with diseases such as cancer, Parkinson's disease, and Alzheimer's disease were dominant in the type with degradation rate regulation. Interestingly, these diseases are caused by the accumulation of proteins. These results indicated that gene expression is regulated structurally, not arbitrarily, according to the gene function. This funding is indicative of a systematic control of transcription processes at the whole-cell level.
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MicroRNAs are important post-transcriptional regulators in different pathophysiological processes. They typically affect the mRNA stability or translation finally leading to the repression of target gene expression. Notably, it is thought that microRNAs are crucial for regulating gene expression during metabolic-related disorders, such as nonalcoholic fatty liver disease (NAFLD). Several studies identify specific microRNA expression profiles associated to different histological features of NAFLD, both in animal models and in patients. Therefore, specific assortments of certain microRNAs could have enormous diagnostic potentiality. In addition, microRNAs have also emerged as possible therapeutic targets for the treatment of NAFLD-related liver damage. In this review, we discuss the experimental evidence about microRNAs both as potential non-invasive early diagnostic markers and as novel therapeutic targets in NAFLD and its more severe liver complications.
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MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.
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