MicroRNA-modulated autophagic signaling networks in cancer

MicroRNAs (miRNAs) are small, non-coding endogenous RNAs ～22 nucleotides (nt) in length that may play the essential roles for regulation of programed cell death, referring to apoptosis and autophagy. Of note, autophagy is an evolutionarily conserved, multi-step lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles. Accumulating evidence has recently revealed that miRNAs can modulate the autophagic pathways in many pathological processes, most notably cancer. In this review, we focus on highlighting the dual functions of miRNAs as either oncogenes (e.g., miRNA-183, miRNA-376b, miRNA-106a, miRNA-221/222, miRNA-31 and miRNA-34c) or tumor suppressors (e.g., miRNA-30a, miRNA-101 and miRNA-9*) via mediating several autophagic signaling pathways in cancer pathogenesis. Taken together, these findings may uncover the regulatory mechanisms of oncogenic and tumor suppressive miRNAs in autophagy, which would provide a better understanding of miRNA-modulated autophagic signaling networks for future cancer therapeutics.     

Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing

ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. RESULTS: We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA. CONCLUSION: Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.     

microRNAs: Key players in virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.     

MicroRNA as a new player in the cell cycle

MicroRNAs (miRNAs) are a newly identified class of small regulatory non‐coding endogenous RNAs that are ubiquitous from animals to plants and have pivotal functions in nearly all biological and metabolic processes. Increasing evidence shows that miRNAs are also new players regulating many protein‐coding genes and specific pathways during the cell cycle. This review focuses on the functions of miRNAs in the cell cycle of differentiated cells and embryonic stem (ES) cells. Aberrant expression of these cell‐cycle‐related miRNAs may result in carcinogenesis, revealing the potential of miRNAs as therapeutic targets for clinical purposes. J. Cell. Physiol. 225: 296–301, 2010. © 2010 Wiley‐Liss, Inc.     

MicroRNAs: Novel Regulators of Oligodendrocyte Differentiation and Potential Therapeutic Targets in Demyelination-Related Diseases

MicroRNAs (miRNAs or miRs) are a class of endogenous small non-coding RNAs that consist of about 22 nucleotides and play critical roles in various biological processes, including cell proliferation, differentiation, apoptosis, and tumorigenesis. In recent years, some specific miRNA, such as miR-219, miR-138, miR-9, miR-23, and miR-19b were found to participate in the regulation of oligodendrocyte (OL) differentiation and myelin maintenance, as well as in the pathogenesis of demyelination-related diseases (e.g., multiple sclerosis, ischemic stroke, and leukodystrophy). These miRNAs control their target mRNA or regulate the protein levels of some signaling pathways, and participate in OL differentiation and the pathogenesis of demyelination-related diseases. During pathologic processes, the expression levels of specific miRNAs are dynamically altered. Therefore, miRNAs act as diagnostic and prognostic indicators of defects in OL differentiation and demyelination-related diseases, and they can provide potential targets for therapeutic drug development.     

人microRNA相关的遗传变异与肿瘤

微RNA(microRNA,miRNA)是新发现的一类进化上高度保守的重要的转录后调控因子,通过调节基因的表达而参与调控细胞凋亡、增殖及分化等生理过程,同时与肿瘤等疾病的发生发展密切相关。近年来研究发现,miRNA、miRNA生物合成通路基因及miRNA的靶基因结合位点的遗传变异(例如单核苷酸多态性和拷贝数变异等)可影响miRNA调控功能的发挥,并产生显著的遗传学效应。文章主要综述了miRNA相关的遗传变异与肿瘤易感性和临床转归等的研究进展。     

应用生物信息学寻找山羊新的microRNA分子及其实验验证

摘要: microRNA(miRNA)是一类长约22个碱基的非编码RNA分子, 在转录后水平调节基因的表达及其在细胞的增殖、分化、凋亡等过程中起着重要的调控作用。根据miRNA分子具有一定的保守性, 文章将人、小鼠、牛、猪和狗5种哺乳动物已知的miRNA分子与NCBI公布的与山羊具有极高同源性的绵羊基因组序列对比, 获得11条miRNA候选分子, 然后通过逆转录聚合酶链反应(RT-PCR)验证, 发现在山羊脑组织中这11条分子均有表达, 肝脏组织中有5条分子表达, 初步确定为山羊新的miRNA分子, 为寻找山羊miRNA提供了新的 思路。     

微RNA-101在肿瘤中的作用

微RNA(microRNA)是内源性发挥转录后调控功能的单链小RNA,种类繁多,在细胞周期调控、凋亡调控、肿瘤的进展等方面起重要作用。近期研究发现,微RNA在功能上表现为癌基因与抑癌基因与前列腺癌、膀胱癌、肝癌、乳腺癌等肿瘤的发生、发展关系密切。EZH2基因的生物学行为与癌基因类似,微RNA-101主要通过调控EZH2的表达量和表观遗传学特征调控其功能。微RNA-101的缺失或表达下调促使组织细胞分裂、增殖,最终可能导致肿瘤的发生与浸润。因此,探寻微RNA-101的生物学作用具有重要意义。     

Diacylglycerol, phosphatidic acid, and the converting enzyme, diacylglycerol kinase, in the nucleus

There exists phosphoinositide (PI) cycle in the nucleus, which is operated differentially from the classical PI cycle at the plasma membrane. Evidence has been accumulated that nuclear PIs and the related enzymes are closely involved in a variety of nuclear processes, although the details remain to be elucidated. In this mini review, some components of PI cycle, i.e., diacylglycerol, phosphatidic acid, and the converting enzyme, diacylglycerol kinase, in the nucleus are discussed with focusing on the lipid metabolism, cell cycle regulation, and animal models.     

Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells

The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.