- RNA modifications and cancer
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Extracellular vesicles in disease
- Cancer Research and Treatments
- Hepatitis B Virus Studies
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Hepatitis C virus research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Nuclear Structure and Function
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Genetic factors in colorectal cancer
- Nutrition, Genetics, and Disease
- Genomics, phytochemicals, and oxidative stress
- Peptidase Inhibition and Analysis
- Cardiovascular Disease and Adiposity
The University of Tokyo
2018-2024
Columbia University
2024
Japan Society for the Promotion of Science
2021-2022
Hitachi General Hospital
2017
Hepatitis B virus (HBV) infection is a major health concern worldwide. Although currently used nucleos(t)ide analogs efficiently inhibit viral replication, proteins transcribed from the episomal covalently closed circular DNA (cccDNA) minichromosome continue to be expressed long-term. Because high RNA or antigen loads may play biological role during this chronicity, elimination of products an ultimate goal HBV treatment. regulatory protein X (HBx) was recently found promote transcription...
This study investigates Actinomyces odontolyticus's role in colorectal cancer initiation.The bacterium secretes lipoteichoic acid-rich membrane vesicles, inducing chronic inflammation, nuclear factor-κB signaling, and excessive reactive oxygen species colonic epithelial cells.These processes result DNA damage, potentially contributing to development.
HBV causes hepatocellular carcinoma (HCC). While it was recently shown that the ability of X protein (HBx) to impair Smc5/6 (structural maintenance chromosome 5/6) complex is important for viral transcription, HBx also a potent driver HCC. However, mechanism by which expression induces hepatocarcinogenesis unclear.Degradation and accumulation DNA damage were observed in both vivo vitro infection models. Rescue experiments performed using nitazoxanide (NTZ), inhibits degradation...
Hepatitis B virus (HBV) infection is a major health concern worldwide. To prevent HBV-related mortality, elimination of viral proteins considered the ultimate goal HBV treatment; however, currently available nucleos(t)ide analogs rarely achieve this goal, as transcription from episomal covalently closed circular DNA (cccDNA) not prevented. regulatory protein X was recently found to target structural maintenance chromosomes 5/6 (Smc5/6) for ubiquitination and degradation by DDB1-CUL4-ROC1 E3...
// Kazuma Sekiba 1 , Motoyuki Otsuka Motoko Ohno Takahiro Kishikawa Mari Yamagami Tatsunori Suzuki Rei Ishibashi Seimiya Eri Tanaka and Kazuhiko Koike Department of Gastroenterology, Graduate School Medicine, The University Tokyo, Tokyo 113-8655, Japan Correspondence to: Otsuka, email: otsukamo-tky@umin.ac.jp Keywords: HBV; cccDNA; minicircle; primary hepatocytes; digital PCR; Immunology Received: February 28, 2018 Accepted: March 24, Published: April 20, 2018...
Human satellite II (HSATII), composed of tandem repeats in pericentromeric regions, is aberrantly transcribed epithelial cancers, particularly pancreatic cancer. Dysregulation repetitive elements cancer tissues can facilitate incidental double-stranded RNA (dsRNA) formation; however, it remains controversial whether dsRNAs play tumor-promoting or tumor-suppressing roles during progression. Therefore, we focused on the formation HSATII and explored its molecular function. The overexpression...
Abstract Mutational activation of the KRAS gene occurs in almost all pancreatic ductal adenocarcinoma (PDAC) and is earliest molecular event their carcinogenesis. Evidence has accumulated metabolic reprogramming PDAC, such as amino acid homeostasis autophagic flux. However, biological effects mutation on at earlier stages PDAC carcinogenesis are unclear. Here we report dynamic immortalized human non-cancerous epithelial cells, which a was induced by gene-editing, may mimic early Similar to...
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to the difficulty of its diagnosis. Because human satellite II (HSATII) RNA, repeat is highly and specifically expressed in PDAC, serum HSATII RNA level may be biomarker PDAC. To measure with high sensitivity reproducibility, we previously developed convenient method, tandem amplification by nuclease protection (TRAP) combined droplet digital PCR (ddPCR). Here, refined original method simultaneously measuring miR-21-5p enhance...
Transcripts from the human
Highly repetitive tandem arrays such as satellite sequences in the centromeric and pericentromeric regions of chromosomes, which were previously considered to be silent, are actively transcribed various biological processes, including cancers. In pancreas, this aberrant expression occurs even Kras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, precancerous lesions. To determine role RNAs carcinogenesis vivo, we constructed mouse major (MajSAT) RNA-expressing transgenic mice....
During cellular aging, many changes in functions occur. A hallmark of aged cells is secretion inflammatory mediators, which collectively referred to as the senescence-associated secretory phenotype (SASP). However, mechanisms underlying such are unclear. Canonically, expression interferon (IFN)-stimulated genes (ISGs) induced by IFNs through formation tripartite transcriptional factor ISGF3, composed IRF9 and phosphorylated forms STAT1 STAT2. this study, constitutive ISGs human-derived...
Although the detection of circulating tumor cells (CTCs) should be crucial for future personalized medicine, no efficient and flexible methods have been established. The current study established a polymeric custom-made chip capturing CTCs with high efficiency flexibility. As an example clinical application, effects self-expandable metallic stent (SEMS) placement on release cancer into blood patients colorectal bowel obstruction were analyzed. This was assessed as SEMS may cause mechanical...
Extracellular vesicles (EVs) released from cells into the blood facilitate intercellular communication and serve as new biomarkers to understand pathophysiology of several conditions. Although importance cargo inside EVs has been extensively studied, sizes that vary with different types cancers are relatively poorly explored. Here, we show pancreatic cancer cell-derived significantly smaller than non-cancer EVs. The size distribution these was confirmed by specifically isolating examining...
Abstract MICA/B proteins are expressed on the surface of various types stressed cells, including cancer cells. Cytotoxic lymphocytes expressing natural killer group 2D (NKG2D) receptor recognize and eliminate However, cells evade such immune recognition by inducing proteolytic shedding proteins. Therefore, preventing could enhance antitumor immunity. Here, screening a protease inhibitor library, we found that fatty-acid amide hydrolase (FAAH) inhibitor, URB597, suppresses MICA/B. URB597...
Extracellular vesicles (EVs) produced by various cells, including tumor carry biomolecules to neighboring cells. In hepatocellular carcinoma (HCC), adenosine inosine RNA editing of antizyme inhibitor 1 (AZIN1), specifically regulated deaminase acting on RNA‑1 (ADAR1), promotes carcinogenesis. The present study examined if EVs and ADAR1 in the released from HCC cells are transferred co‑culture systems reporter assay. Distribution expression human tissues were immunohistochemistry. containing...