Dataset Information

Oncoviruses and Pathogenic MicroRNAs in Humans.

ABSTRACT: For disease prognosis, the functional significance of the oncoviral integration locus in oncogenesis has remained enigmatic. The locus encodes several transcripts without protein products, but microRNAs (miRNAs) have recently been identified from a common oncoviral integration locus. miRNA is an endogenous, non-coding small RNA by which gene expression is suppressed. Although miRNA genes, such as let-7 in the nematode, have orthologs among animals, the relationship between miRNAs and tumorigenesis or tumor suppression has been mainly discovered in several human cancers. On the contrary, this review clearly demonstrates the potential for human tumorigenesis of both miRNA genes from oncoviral integration sites and other cellular onco-microRNA genes, and we conclude that alteration of the miRNA profile of cells can be defined as tumorigenic or tumor suppressive. Thus, we explain here that virally-pathogenic miRNAs could also be partly responsible for oncogenesis or oncogene suppression to confirm' the RNA wave', with the miRNAs hypothesized as a mobile and functional genetic element.

SUBMITTER: Fujii YR

PROVIDER: S-EPMC2778015 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Oncoviruses and Pathogenic MicroRNAs in Humans.

Fujii Yoichi Robertus YR

The open virology journal 20090507

For disease prognosis, the functional significance of the oncoviral integration locus in oncogenesis has remained enigmatic. The locus encodes several transcripts without protein products, but microRNAs (miRNAs) have recently been identified from a common oncoviral integration locus. miRNA is an endogenous, non-coding small RNA by which gene expression is suppressed. Although miRNA genes, such as let-7 in the nematode, have orthologs among animals, the relationship between miRNAs and tumorigenes ...[more]

PMID: 19920887

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Project description:Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.

Project description:Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease driven by genetic and environmental factors. MicroRNAs (miRNAs) serve as pleiotropic post-transcriptional regulators of cellular pathways. Although several miRNAs have been associated with NAFLD and fibrosis, there are limited studies in humans examining their differential association with pathogenic factors or histological features of NAFLD. We examined the differential relationships of five of the best-described circulating microRNAs (miR-34a, miR-122, miR-191, miR-192, and miR-200a) with histological features and pathogenic factors of NAFLD. A cross-sectional study was conducted to examine the relationship between relative levels of circulating microRNAs standardized by z-scores and histological features of NAFLD, common NAFLD genetic polymorphisms, and insulin resistance measured by the enhanced lipoprotein insulin resistance index in 132 subjects with biopsy-proven NAFLD. We found that miR-34a, miR-122, miR-192, miR-200a, but not miR-191, strongly correlate with fibrosis in NAFLD by increases of 0.20 to 0.40 SD (P < 0.005) with each stage of fibrosis. In multivariate analysis, miR-34a, miR-122, and miR-192 levels are independently associated with hepatic steatosis and fibrosis, but not lobular inflammation or ballooning degeneration, whereas miR-200a is only associated with fibrosis. Among the four miRNAs, miR-34a, miR-122, and miR-192 are associated with pathogenic factors of NAFLD, including insulin resistance measured by eLP-IR, patatin-like phospholipase domain containing 3 I148M, and transmembrane 6 superfamily 2 (TM6SF2) E167K polymorphisms. In contrast, miR-200a is only associated with the TM6SF2 E167K variant. Finally, miR-34a has the strongest predictive value for various stages of fibrosis, with C-statistic approximates-combined predictive score for miRNAs. Conclusion: miR-34a, miR-122, miR-192, and miR-200a demonstrate strong associations with NAFLD severity by histology, but differential associations with pathogenic factors.

Dataset Information

Oncoviruses and Pathogenic MicroRNAs in Humans.

Publications

Oncoviruses and Pathogenic MicroRNAs in Humans.

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