Abstract:
:Liver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Pparγ and thus we identify a role of Pparγ as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.
journal_name
Proc Natl Acad Sci U S Aauthors
Winkler I,Bitter C,Winkler S,Weichenhan D,Thavamani A,Hengstler JG,Borkham-Kamphorst E,Kohlbacher O,Plass C,Geffers R,Weiskirchen R,Nordheim Adoi
10.1073/pnas.1909145117subject
Has Abstractpub_date
2020-01-07 00:00:00pages
454-463issue
1eissn
0027-8424issn
1091-6490pii
1909145117journal_volume
117pub_type
杂志文章abstract::Androgen independence is responsible for most prostate cancer lethality, yet currently there are no effective clinical treatments. We have been investigating the mechanisms underlying androgen-independent prostate cancer in Nkx3.1;Pten mutant mice, which display salient features of the disease, including a requirement...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0606836103
更新日期:2006-09-26 00:00:00
abstract::Although current theories of color vision differ in many respects, they all assume the existence of a uniquely defined neutral point in chromaticity space. It generally is assumed that this point satisfies several criteria simultaneously. One of these criteria is that it is perceived as achromatic. A further criterion...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.192216699
更新日期:2002-10-01 00:00:00
abstract::To test directly whether fibrin(ogen) is a key binding site for apolipoprotein(a) [apo(a)] in vessel walls, apo(a) transgenic mice and fibrinogen knockout mice were crossed to generate fibrin(ogen)-deficient apo(a) transgenic mice and control mice. In the vessel wall of apo(a) transgenic mice, fibrin(ogen) deposition ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.21.12591
更新日期:1998-10-13 00:00:00
abstract::The Lyz endolysin of bacteriophage P1 was found to cause lysis of the host without a holin. Induction of a plasmid-cloned lyz resulted in lysis, and the lytic event could be triggered prematurely by treatments that dissipate the proton-motive force. Instead of requiring a holin, export was mediated by an N-terminal tr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0400957101
更新日期:2004-04-27 00:00:00
abstract::Misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1) is implicated in neuronal death in amyotrophic lateral sclerosis. Each SOD1 monomer binds to 1 copper and 1 zinc ion and maintains its disulfide bond (Cys-57-Cys-146) in the reducing cytoplasm of cell. Mounting experimental evidence suggests that metal l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803266105
更新日期:2008-12-16 00:00:00
abstract::Adults and older children are more likely to punish a wrongdoer for a moral transgression when the victim belongs to their group. Building on these results, in violation-of-expectation experiments (n = 198), we examined whether 2.5-year-old toddlers (Exps. 1 and 2) and 1-year-old infants (Exps. 3 and 4) would selectiv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1817849116
更新日期:2019-03-26 00:00:00
abstract::Receptor-binding specificity of HA, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Influenza type B virus almost exclusively infects humans and contributes to the annual "flu" sickness. Here we report the structures of influenza B virus HA in complex ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0708363104
更新日期:2007-10-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1718953115
更新日期:2018-10-23 00:00:00
abstract::The catalytic generation of chiral ester enolate equivalents from α,β-unsaturated aldehydes with chiral N-hetereocyclic carbene catalysts makes possible highly enantioselective hetero-Diels-Alder reactions. The reactions proceed under simple, mild conditions with both aliphatic and aromatic substituted enals as substr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1007469107
更新日期:2010-11-30 00:00:00
abstract::The diversity of the T cell receptor (TCR) repertoire is limited, because of the processes of positive and negative T cell selection. To obtain T cells with specificities beyond the immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, a library of T cell variants is gene...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.26.14578
更新日期:2000-12-19 00:00:00
abstract::The antiangiogenic agent fumagillin (Fg) and its analog TNP-470 bind to intracellular metalloprotease methionine aminopeptidase-2 (MetAP-2) and inhibit endothelial cell growth in a p53-dependent manner. To confirm the role of MetAP-2 in endothelial cell proliferation and to validate it as a physiological target for th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0511313103
更新日期:2006-07-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0809558105
更新日期:2008-12-30 00:00:00
abstract::In both human patients and murine models, the progression from insulitis to diabetes is neither immediate nor inevitable, as illustrated by the innocuous versus destructive infiltrates of BDC2.5 transgenic mice on the nonobese diabetic (NOD) versus C57BL/6.H-2g7 genetic backgrounds. Natural killer (NK)-cell-specific t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402065101
更新日期:2004-05-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1306447110
更新日期:2013-10-08 00:00:00
abstract::Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.10.3773
更新日期:1990-05-01 00:00:00
abstract::Two-dimensional 1H NMR investigations were used to locate elements of regular secondary structure in the human complement protein C3a (the des-Arg77 derivative) in solution. The results were compared to a refined crystal structure based on the 3.2-A resolution structure of des-Arg77-C3a [Huber, R., Scholze, H., Paques...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.14.5036
更新日期:1988-07-01 00:00:00
abstract::An endogenous circadian biological clock controls the temporal aspects of life in most organisms, including rhythmic control of genes involved in clock output pathways. In the fungus Neurospora crassa, one pathway known to be under control of the clock is asexual spore (conidia) development. To understand more fully t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.23.13096
更新日期:1996-11-12 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.8.2604
更新日期:1976-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.26.12676
更新日期:1994-12-20 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501253102
更新日期:2005-04-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717100115
更新日期:2018-01-02 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0812604106
更新日期:2009-03-31 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.7.2351
更新日期:1989-04-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906636106
更新日期:2009-12-22 00:00:00
abstract::The active conformation of native peroxisomal 3-ketoacyl-CoA thiolases (EC 2.3.1.16) is homodimeric. We have previously shown that a truncated Saccharomyces cerevisiae thiolase lacking its first 16 N-terminal amino acids fails to be translocated into peroxisomes but assembles into an enzymatically active form in the c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.22.10541
更新日期:1994-10-25 00:00:00
abstract::3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepine-3-yl)-1H-indole-2-carboxamide (L-364,718) interacted in a competitive manner with rat pancreatic cholecystokinin (CCK) receptors as determined by Scatchard analysis of the specific binding of 125I-labeled CCK. The affinity of L-364,718 for both pancre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.13.4923
更新日期:1986-07-01 00:00:00
abstract::The COVID-19 pandemic is a shocking reminder of how our world would look in the absence of vaccination. Fortunately, new technologies, the pace of understanding new and existing pathogens, and the increased knowledge of the immune system allow us today to develop vaccines at an unprecedented speed. Some of the vaccine...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2020368118
更新日期:2021-01-19 00:00:00
abstract::We have developed a low stringency polymerase chain reaction (LSPCR) to isolate the unknown neighboring region around a known DNA sequence, thus allowing efficient targeted gene walking. The method involves the polymerase chain reaction (PCR) with a single primer under conditions of low stringency for primer annealing...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.8.2975
更新日期:1994-04-12 00:00:00
abstract::The optical transitions of a chiral, three-substituted polythiophene with an amino acid function can be tuned by interactions with synthetic peptides. The addition of a positively charged peptide with a random-coil formation will force the polymer to adopt a nonplanar conformation, and the intensity of the emitted lig...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1834422100
更新日期:2003-09-02 00:00:00
abstract::N-type Ca2+ channels mediate Ca2+ influx, which initiates fast exocytosis of neurotransmitters at synapses, and they interact directly with the SNARE proteins syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) through a synaptic protein interaction (synprint) site in the intracellular loop connecting doma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.10.5405
更新日期:1997-05-13 00:00:00