A5059765912- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- interferon and immune responses
- Adipose Tissue and Metabolism
- DNA and Nucleic Acid Chemistry
- RNA regulation and disease
- CRISPR and Genetic Engineering
- melanin and skin pigmentation
- Ubiquitin and proteasome pathways
- Angiogenesis and VEGF in Cancer
- DNA Repair Mechanisms
- Cancer Research and Treatments
- Neonatal Health and Biochemistry
- Skin Protection and Aging
- TGF-β signaling in diseases
- Immune Cell Function and Interaction
- Cancer-related gene regulation
University of Tsukuba
1997-2025
The University of Tokyo
2002-2023
National Institute of Advanced Industrial Science and Technology
2013-2023
Saitama International Medical Center
2008-2009
St. Marianna University School of Medicine
2004
Hokkaido University
2004
Molina Center for Energy and the Environment
2004
Institute of Applied Biochemistry
1997-2003
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
2001-2003
Alliance University
2000
Abstract The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type IFN. RIG-I contains domain that belongs to DExD/H-box helicase family exhibits an N-terminal caspase recruitment (CARD) homology. There are three genes encoding RIG-I-related proteins in human mouse genomes. Melanoma differentiation associated 5 (MDA5), which consists CARD domain, functions as positive...
Longevity regulatory genes include the Forkhead transcription factor FOXO and NAD-dependent histone deacetylase silent information regulator 2 (Sir2). Genetic studies demonstrate that Sir2 acts to extend lifespan in Caenorhabditis elegans upstream of DAF-16, a member family, insulin-like signaling pathway. However, molecular mechanisms underlying requirement DAF-16 activity Sir2-mediated longevity remain unknown. Here we show reversible acetylation Foxo1 (also known as FKHR), mouse ortholog,...
Background Nrf2 belongs to the Cap‐N‐Collar (CNC) transcription factor family and is essential for antioxidant responsive element (ARE)‐mediated expression of a group detoxifying genes. The forced in mammalian cells activates target genes through ARE, with showing highest transactivation activity among CNC factors. To elucidate molecular mechanisms generating this potent activity, we examined functions domains within Nrf2. Result We found that contains two activation domains, Neh4 Neh5,...
We recently demonstrated that human melanocyte proliferation and differentiation could be stimulated by endothelin (ET) derivatives via a receptor-mediated signal transduction pathway (Yada, Y., Higuchi, K., Imokawa, G. (1991) J. Biol. Chem. 266, 18352-18357). show here the growth factors for melanocytes are produced secreted surrounding cells, namely keratinocytes ET-1 Big-ET-1. Northern blots have revealed presence of gene transcripts in proliferating keratinocytes. The production...
OBJECTIVE To identify novel type 2 diabetes gene variants and confirm previously identified ones, a three-staged genome-wide association study was performed in the Japanese population. RESEARCH DESIGN AND METHODS In stage 1 scan, we genotyped 519 case 503 control subjects with 482,625 single nucleotide polymorphism (SNP) markers; panel comprising 1,110 1,014 subjects, assessed 1,456 SNPs (P < 0.0025, 1); additionally to direct genotyping, 964 healthy formed silico panel. Along...
Estrogen is a key regulator of normal function female reproductive system and plays pivotal role in the development progression breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes component estrogen signaling pathway. expressed high proportion human tumors, expression levels significantly correlate with receptor (ER) positivity. In addition, 17-beta-estradiol (E2) induces an ERα dependent manner. interacts components SWI/SNF-B chromatin remodeling complex....
RNA interference appears to be a potentially powerful tool for studies of genes unknown function. However, differences in efficacy at different target sites remain problematic when small interfering (siRNA) is used as an effector. Similar problems are associated with attempts gene inactivation using antisense oligonucleotides (ODNs) and ribozymes. We performed comparative analysis the suppressive effects three knockdown methods, namely, methods based on (RNAi), ODNs, ribozymes, luciferase...
The interaction between the chemokine receptor CXCR4 and its specific ligand, stromal cell-derived factor-1 (SDF-1/CXCL12), mediates several cellular functions. In cancer, SDF-1-positive or CXCR4-positive cells of various lineages are detected within tumor tissues. Recent intensive research has indicated possibility that blocking could reduce metastatic potential cancer cells. Here, we show inhibition SDF-1/CXCR4 axis decreases growth s.c. gastrointestinal tumors through suppression...
Abstract IFN regulatory factor 3 (IRF-3) is a critical transcription that regulates an establishment of innate immune status following detection viral pathogens. Recent studies have revealed two IκB kinase (IKK)-like kinases, NF-κB-activating kinase/Traf family member-associated NF-κB activator-binding 1 and IKK-i/IKKε, are responsible for activation IRF-3, but the mechanism IRF-3 signaling pathway has not been fully understood. In this study, we report suppressed by A20, which was initially...
Gene targeting using short interfering RNA (siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. For the application siRNA technology therapy, however, still more efficient transduction into target cells is needed. In this study, we developed an adenoviral vector harboring tandem-type expression unit, in which sense antisense strands composing duplex were separately transcribed by two human U6 promoters. Targeting survivin,...
Abstract Tumor cells alter their metabolism to meet demand for macromolecules and support a high rate of proliferation as well cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types tumors crucial tumor cell metastasis. However, its role metabolic reprogramming poorly understood. Here, we show that YY1 alters by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme pentose phosphate pathway. By stimulating pathway,...
The paracrine linkage of endothelins (ET) between keratinocytes and melanocytes suggested that ETs are intrinsic mediators for human in UVB-induced pigmentation. In this study, the role ET-1 epidermal hyperpigmentation was investigated vivo vitro. addition 10 nM induced a H-7 (10 microM) suppressible-increase tyrosinase activity cultured accompanied by elevated levels tyrosinase-related protein-1 mRNA expression as shown Northern blotting. Analysis signaling mechanisms leading to activation...
Abstract Background RNA interference (RNAi) is a phenomenon in which expression of an individual gene can be specifically silenced by introducing double‐stranded RNA, one complementary to the gene, into cells. This observed mammalian cells when small interfering RNAs (siRNAs) are used, and receiving attention as most powerful tool for reverse genetics post genome era. Several groups have developed vector‐based siRNA‐expression systems that induce RNAi living Methods We describe here...
In human papillary thyroid cancers (PTCs), mutations of RET/PTC, NTRK, RAS, or BRAF are found in about two thirds cases with practically no overlap, providing genetic evidence that constitutive signaling along RET-RAS-BRAF-MAPK is key to their development. The requirement for RET/PTC-mediated MAPK activation and gene expression has not been tested functionally. There three RAF isoforms: ARAF, BRAF, CRAF. Compared the others, ARAF a much weaker stimulator MAPK. To determine isoform mediating...
Short interfering RNAs (siRNAs) are valuable reagents for sequence-specific inhibition of gene expression via the RNA interference (RNAi) pathway. Although it has been proposed that relative thermodynamic stability at 5′-ends siRNAs plays a crucial role in siRNA strand selection, we demonstrate here character 2-nt 3′-overhang is predominant determinant which participates RNAi We show with unilateral on antisense more effective than 3′-overhangs both ends, due to preferential loading into...
STAT3 signaling constitutes an important negative feedback mechanism for the maintenance of immune homeostasis, a suppressive signal Th1 response in murine macrophages, and cancer evasion various cells. The strategy inhibition should be considered, because these features could impede effective immunotherapy. We have evaluated effects inactivation dendritic cells (DCs) on responses mice humans. DCs derived from LysMcre/STAT3(flox/flox) displayed higher cytokine production to TLR stimulation,...
In response to hypoxic stress, hypoxia-inducible factor (HIF)-1α is a critical transcription regulating fundamental cellular processes, and its elevated expression level activity are associated with poor outcomes in most malignancies. The Yin Yang 1 (YY1) an important negative regulator of the tumor suppressor p53. However, role YY1 under condition poorly understood. Herein, we show that inhibition reduced accumulation HIF-1α condition, consequently downregulated target genes. Interestingly,...