microRNA——新的髓系白血病致病因子及临床标物

微RNA(MicroRNA,miRNA)是一类长18～25 nt的非编码RNA,主要通过与靶基因mRNA3'UTR上的互补区域结合后在转录后水平(RNA切割或翻译抑制)负性调控靶基因的表达.现已发现,miRNA参与了多种正常细胞过程以及肿瘤发生的调控.miRNA也在造血链系分化和相关白血病中发挥重要作用.急性髓系白血病...     

miRNAs在肝癌干细胞中的作用

MicroRNAs (miRNAs)是一类参与转录后调控的小分子RNA,它在调控细胞的增殖、分化及肿瘤的形成等多种生理及病理过程中发挥着重要的作用.肝癌干细胞是肝癌组织中具有自我更新能力和分化潜能的一个微群体,它能够启始肝癌的发生,并且与肝癌的抗药性及复发等密切相关.已经有研究表明miRNAs对肝癌干细胞的发生发展起着重要的调控作用,包括致癌和抑癌的作用,因此总结miRNAs在肝癌干细胞中作用,有助于更好理解肝癌干细胞的特性及肝癌肿瘤生物学.近年来,除了传统的分子生物学手段,组学和系统生物学研究策略的运用也为miRNAs在肝癌中的研究提供了新的思路.鉴于此,深入研究miRNAs在肝癌干细胞中的分子机制,将为靶向肝癌干细胞的临床治疗提供新的途径.     

Big roles of microRNAs in tumorigenesis and tumor development

MicroRNAs (miRNAs) are a class of endogenous non-protein-coding small RNAs that are evolutionarily conserved and widely distributed among species. Their major function is to negatively regulate target gene expression. A single miRNA can regulate multiple target genes, indicating that miRNAs may regulate multiple signaling pathways and participate in a variety of physiological and pathological processes. Currently, approximately 50% of identified human miRNA-coding genes are located at tumor-related fragile chromosome regions. Abnormal miRNA expression and/or mutations have been found in almost all types of malignancies. These abnormally expressed miRNAs play roles similar to tumor suppressor genes or oncogenes by regulating the expression and/or function of tumor-related genes. Therefore, miRNAs, miRNA target genes, and the genes regulating miRNAs form a regulatory network with miRNAs in the hub. This network plays a pivotal role in tumorigenesis and tumor development.     

Regulation of micro-RNA,epigenetic factor by natural products for the treatment of cancers: Mechanistic insight and translational association

From onset to progression, cancer is a ailment that might take years to grow. All common epithelial malignancies, have a long latency period, frequently 20 years or more, different gene may contain uncountable mutations if they are clinically detectable. MicroRNAs (miRNAs) are around 22nt non-coding RNAs that control gene expression sequence-specifically through translational inhibition or messenger degradation of RNA (mRNA). Epigenetic processes of miRNA control genetic variants through genomic DNA methylation, post-translation histone modification, rework of the chromatin, and microRNAs. The field of miRNAs has opened a new era in understanding small non-coding RNAs since discovering their fundamental mechanisms of action. MiRNAs have been found in viruses, plants, and animals through molecular cloning and bioinformatics approaches. Phytochemicals can invert the epigenetic aberrations, a leading cause of the cancers of various organs, and act as an inhibitor of these changes. The advantage of phytochemicals is that they only function on cells that cause cancer without affecting normal cells. Phytochemicals appear to play a significant character in modulating miRNA expression, which is linked to variations in oncogenes, tumor suppressors, and cancer-derived protein production, according to several studies. In addition to standard anti-oxidant or anti-inflammatory properties, the initial epigenetic changes associated with cancer prevention may be modulated by many polyphenols. In correlation with miRNA and epigenetic factors to treat cancer some of the phytochemicals, including polyphenols, curcumin, resveratrol, indole-3-carbinol are studied in this article.     

Expression signatures of intragenic miRNAs and their corresponding host genes in myeloid leukemia cells

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in gene regulation. Approximately half of miRNAs are located within known genes and called intragenic miRNAs. 408 human intragenic miRNAs and their corresponding host genes were analyzed for genomic organization and functional characterization. Using quantitative real-time PCR, the expression levels of a subset of intragenic miRNAs and their host genes were examined in diverse myeloid leukemia cell lines, and their regulation in response to pharmacological stimuli was also evaluated. Expression of miR-22 strongly correlated with both myeloid leukemia subtypes and the expression of its host gene C17orf91 (p?<?0.05). The latter was absent in hematopoietic progenitors but abundant in erythroid and monocytic lineages. These results demonstrated that the expression signatures of miR-22 and C17orf91 are associated with developmental lineages and specific leukemia subtypes.     

Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA（miRNA） expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia（AML） cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia（CML） cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.     

Downregulation of miR-31, miR-155, and miR-564 in chronic myeloid leukemia cells

Background/Aims

MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. However, little is known about the role of miRNAs in chronic myeloid leukemia (CML). Our objective is to decipher a miRNA expression signature associated with CML and to determine potential target genes and signaling pathways affected by these signature miRNAs.

Results

Using miRNA microarrays and miRNA real-time PCR we characterized the miRNAs expression profile of CML cell lines and patients in reference to non-CML cell lines and healthy blood. Of all miRNAs tested, miR-31, miR-155, and miR-564 were down-regulated in CML cells. Down-regulation of these miRNAs was dependent on BCR-ABL activity. We next analyzed predicted targets and affected pathways of the deregulated miRNAs. As expected, in K562 cells, the expression of several of these targets was inverted to that of the miRNA putatively regulating them. Reassuringly, the analysis identified CML as the main disease associated with these miRNAs. MAPK, ErbB, mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) were the main molecular pathways related with these expression patterns. Utilizing Venn diagrams we found appreciable overlap between the CML-related miRNAs and the signaling pathways-related miRNAs.

Conclusions

The miRNAs identified in this study might offer a pivotal role in CML. Nevertheless, while these data point to a central disease, the precise molecular pathway/s targeted by these miRNAs is variable implying a high level of complexity of miRNA target selection and regulation. These deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of CML, and propose possible new avenues for therapeutic treatment.     

microRNAs - powerful repression comes from small RNAs

microRNAs (miRNAs) encode a novel class of small, non-coding RNAs that regulate gene expression post-trancriptionally. miRNAs comprise one of the major non-coding RNA families, whose diverse biological functions and unusual capacity for gene regulation have attracted enormous interests in the RNA world. Over the past 16 years, genetic, biochemical and computational approaches have greatly shaped the growth of the field, leading to the identification of thousands of miRNA genes in nearly all metazoans. The key molecular machinery for miRNA biogenesis and silencing has been identified, yet the precise biochemical and regulatory mechanisms still remain elusive. However, recent findings have shed new light on how miRNAs are generated and how they function to repress gene expression. miRNAs provide a paradigm for endogenous small RNAs that mediate gene silencing at a genome-wide level. The gene silencing mediated by these small RNAs constitutes a major component of gene regulation during various developmental and physiological processes. The accumulating knowledge about their biogenesis and gene silencing mechanism will add a new dimension to our understanding about the complex gene regulatory networks.     

Comparison of microRNAs in adipose and muscle tissue from seven indigenous Chinese breeds and Yorkshire pigs

Elucidation of the pig microRNAome is essential for interpreting functional elements of the genome and understanding the genetic architecture of complex traits. Here, we extracted small RNAs from skeletal muscle and adipose tissue, and we compared their expression levels between one Western breed (Yorkshire) and seven indigenous Chinese breeds. We detected the expression of 172 known porcine microRNAs (miRNAs) and 181 novel miRNAs. Differential expression analysis found 92 and 12 differentially expressed miRNAs in adipose and muscle tissue respectively. We found that different Chinese breeds shared common directional miRNA expression changes compared to Yorkshire pigs. Some miRNAs differentially expressed across multiple Chinese breeds, including ssc‐miR‐129‐5p, ssc‐miR‐30 and ssc‐miR‐150, are involved in adipose tissue function. Functional enrichment analysis revealed that the target genes of the differentially expressed miRNAs are associated mainly with signaling pathways rather than metabolic and biosynthetic processes. The miRNA–target gene and miRNA–phenotypic traits networks identified many hub miRNAs that regulate a large number of target genes or phenotypic traits. Specifically, we found that intramuscular fat content is regulated by the greatest number of miRNAs in muscle tissue. This study provides valuable new candidate miRNAs that will aid in the improvement of meat quality and production.     

Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure

As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.     

Small RNA profiling in two Brassica napus cultivars identifies microRNAs with oil production- and development-correlated expression and new small RNA classes

MicroRNAs (miRNAs) and small interfering RNAs are important regulators of plant development and seed formation, yet their population and abundance in the oil crop Brassica napus are still not well understood, especially at different developmental stages and among cultivars with varied seed oil contents. Here, we systematically analyzed the small RNA expression profiles of Brassica napus seeds at early embryonic developmental stages in high-oil-content and low-oil-content B. napus cultivars, both cultured in two environments. A total of 50 conserved miRNAs and 9 new miRNAs were identified, together with some new miRNA targets. Expression analysis revealed some miRNAs with varied expression levels in different seed oil content cultivars or at different embryonic developmental stages. A large number of 23-nucleotide small RNAs with specific nucleotide composition preferences were also identified, which may present new classes of functional small RNAs.