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September 2014 - April 2019
August 2007 - August 2014
Publications
Publications (91)
The thyroid gland plays a critical role in the maintenance of whole body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocr...
Background:
Early-onset colorectal cancer (EOCRC) has been increasing in incidence worldwide but its genomic pathogenesis is mostly undetermined. This study aimed to identify robust EOCRC-specific gene expression patterns in non-familial adenomatous polyposis (FAP) and non-hereditary nonpolyposis colorectal cancer syndrome (HNPCC) EOCRC.
Method:...
The loss-of-function variants are thought to be associated with inflammation in the stomach. We here aimed to evaluate the extent and role of methylation at the SSTR2 promoter in inflammation and gastric tumor formation. A whole-genome bisulfite sequencing analysis revealed that the SSTR2 promoter was significantly hypermethylated in gastric tumors...
Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain uncle...
The roles of the serine/glycine metabolic pathway (SGP) have recently been evident in certain types of tumor physiology; however, the pathological relevance of SGP in undifferentiated thyroid cancer remains unexplored. Herein, we employed a comparative transcriptome analysis of bulk RNA sequencing coupled with single-cell RNA sequencing, showing th...
Objectives.Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusion, and recurrence markers are still unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer pati...
Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo...
Crohn’s disease (CD) and ulcerative colitis (UC) can be difficult to differentiate. As differential diagnosis is important in establishing a long-term treatment plan for patients, we aimed to develop a machine learning model for the differential diagnosis of the two diseases using RNA sequencing (RNA-seq) data from endoscopic biopsy tissue from pat...
Background
Illumina next generation sequencing (NGS) systems are the major sequencing platform in worldwide next-generation sequencing market. On the other hand, MGI Tech launched a series of new NGS equipment that promises to deliver high-quality sequencing data faster and at lower prices than Illumina’s sequencing instruments.Objective
In this st...
Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. Our previous study showed that global methylation of promoters may increase or decrease during the transition from gastric mucosa to intestinal metaplasia (IM) to gastric cancer (GC). Here, CpG hypomethylation of the serine/threonine kinase STK31 promoter in IM a...
Interferons (IFNs) are a crucial component in the innate immune response. Especially the IFN-β signaling operates in most cell types and plays a key role in the first line of defense upon pathogen intrusion. The induction of IFN-β should be tightly controlled, because its hyperactivation can lead to tissue damage or autoimmune diseases. Activation...
The challenge in managing thyroid nodules is to accurately diagnose the minority of those with malignancy. We aimed to identify diagnostic and prognostic miRNA markers for thyroid nodules. In a discovery cohort, we identified 20 candidate miRNAs to differentiate between noninvasive follicular thyroid neoplasms with papillary-like nuclear features (...
Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. The caudal-type homeobox gene CDX2 is not expressed in normal gastric epithelia but rather in adult intestinal epithelia, and it is overexpressed in intestinal metaplasia (IM). However, it remains unclear how CDX2 transcription is suppressed in normal gastric epi...
nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study a...
Many studies have focused on global hypomethylation or hypermethylation of tumor suppressor genes, but less is known about the impact of promoter hypomethylation of oncogenes. We previously showed that promoter methylation may gradually increase or decrease during the transition from gastric mucosa (GM) to intestinal metaplasia (IM) to gastric canc...
Background:
There are no reliable biomarkers to accurately differentiate indolent thyroid tumors from more aggressive thyroid cancers. This study aimed to develop new DNA methylation markers for diagnosis and recurrence risk stratification of papillary thyroid carcinoma (PTC).
Methods:
Thyroid tumor-specific DNA methylation profiling was investi...
Background
Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity.
Methods
We analyzed RNA-seq-based transcriptome data to identify a...
Currently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Recently, MGI Tech launched a series of new sequencers, including the MGISEQ-2000, which promise to deliver high-quality sequencing data faster and at lower prices than Illumina’s sequencers. In this study, we compared the performan...
The crab-eating monkey is widely used in biomedical research for pharmacological experiments. Epigenetic regulation in the brain regions of primates involves complex patterns of DNA methylation. Previous studies of methylated CpG-binding domains using microarray technology or peak identification of sequence reads mostly focused on developmental sta...
DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells,...
In the original version of the Supplementary Information file associated with this Article, Supplementary Fig. 18 panel b was inadvertently replaced with a duplicate of panel a. The error has now been fixed and the corrected version of the Supplementary Information PDF is available to download from the HTML version of the Article.
Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. Th...
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates an...
Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that...
Although various mechanisms of castration-resistant prostate cancer (CRPC) have been discovered, reliable biomarkers for monitoring CRPC progression are lacking. We sought to identify molecules that predict the progression of advanced prostate cancer (AdvPC) into CRPC. The study used primary-site samples (N=45 for next-generation sequencing (NGS);...
In forensics, short tandem repeat (STR) markers are useful in identifying individuals from biological evidence found at crime scenes. However, they cannot be used to distinguish between genetically identical monozygotic (MZ) twins, causing problems in cases with an MZ twin as a suspect. DNA methylation, which occurs at the 5'-position of cytosine i...
RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III...
RNA polymerase III (Pol III) synthesizes a range of medium-sized noncoding RNAs (collectively ‘Pol III genes’) whose early established biological roles were so essential that they were considered ‘housekeeping genes.’ Besides these fundamental functions, diverse unconventional roles of mammalian Pol III genes have recently
been recognized and their...
Objective
Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical re...
Purpose:
To investigate Helicobacter pylori (H.pylori) associated genome-wide aberrant methylation patterns in gastric mucosa and blood leukocyte DNA, a population-based study was conducted in Linqu County.
Results:
A total of 3000 and 386 CpGs were differentially methylated after successful H.pylori eradication in gastric mucosa and blood leuko...
Due to advances in omics technologies, numerous genome-wide studies on human samples have been published, and most of the omics data with the associated clinical information are available in public repositories, such as Gene Expression Omnibus and ArrayExpress. While analyzing several public datasets, we observed that errors in gender information o...
Peritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We id...
[This corrects the article on p. 70 in vol. 13, PMID: 26523130.].
MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate t...
Recent evidence has shown that the level of 5-hydroxymethylcytosine (5hmC) in chromosomal DNA is aberrantly decreased in a variety of cancers, but whether this decrease is a cause or a consequence of tumorigenesis is unclear. Here we show that, in gastric cancers, the 5hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) exp...
Clinical characteristics of the plasma samples from 35 patients with gastric cancer and 35 healthy controls
Clinical characteristics of the 73 paired gastric cancer tissue samples
MicroRNAs (miRNA) are a class of small (∼22 nucleotides) non-coding RNAs that regulate diverse biological processes at the post-transcriptional level. MiRNAs have great potential for forensic body fluid identification because they are expressed in a tissue specific manner and are less prone to degradation. Previous studies reported several miRNAs a...
nc886, a novel type of non-coding RNA, was initially identified as a microRNA precursor or a vault RNA, but it has been shown to be distinct from them and rather to be a cellular RNA ligand and inhibitor of PKR (Protein Kinase RNA-activated). PKR's roles in viral infection, cellular stresses, and cancer are well documented. nc886 has also been sugg...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
5-hydromethylcytosine (5hmC) is a hydroxmethylated form of DNA cytosine catalyzed by TET proteins. Recently, it was reported that aberrant regulation of 5hmC is associated with many cancers such as breast cancer, glioma, leukemia and melanoma. In this study, we examined the stat...
nc886 is a 101 nucleotide long non-coding RNA that has been designated as a precursor microRNA or a vault RNA based upon it sequence. nc886 has also been suggested to be a tumor suppressor, mainly inferred by its expression pattern as well as its genomic location at human chromosome 5q31, a locus for a tumor suppressor gene(s). However, legitimate...
nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppress...
Forensic Body Fluid Identification by Analysis of Multiple RNA Markers Using NanoString Technology