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- 저자 : Nakayama Mizuho (검색결과 3 건)
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Nakayama Mizuho,Wang Dong,Kok Sau Yee,Hiroko Oshima,Oshima Masanobu 대한암예방학회 2022 Journal of cancer prevention Vol.27 No.1
Comprehensive genome analyses have identified frequently mutated genes in human colorectal cancers (CRC). These include APC, KRAS, SMAD4, TP53, and FBXW7. The biological functions of the respective gene products in cell proliferation and homeostasis have been intensively examined by in vitro experiments. However, how each gene mutation or combinations of specific mutations drive malignant progression of CRC in vivo has not been fully understood. Based on the genomic information, we generated mouse models that carry multiple mutations of CRC driver genes in various combinations, and we performed comprehensive histological analyses to link genetic alteration(s) and tumor phenotypes, including liver metastasis. In this review article, we summarize the phenotypes of the respective genetic models carrying major driver mutations and discuss a possible mechanism of mutations underlying malignant progression.
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Han, Tae-Su,Voon, Dominic Chih-Cheng,Oshima, Hiroko,Nakayama, Mizuho,Echizen, Kanae,Sakai, Eri,Yong, Zachary Wei Ern,Murakami, Kazuhiro,Yu, Liang,Minamoto, Toshinari,Ock, Chan-Young,Jenkins, Brendan J Elsevier 2019 Gastroenterology Vol.156 No.4
<P><B>Background & Aims</B></P> <P>Gastritis is associated with development of stomach cancer, but little is known about changes in microRNA expression patterns during gastric inflammation. Specific changes in gene expression in epithelial cells are difficult to monitor because of the heterogeneity of the tissue. We investigated epithelial cell-specific changes in microRNA expression during gastric inflammation and gastritis-associated carcinogenesis in mice.</P> <P><B>Methods</B></P> <P>We used laser microdissection to enrich epithelial cells from K19-C2mE transgenic mice, which spontaneously develop gastritis-associated hyperplasia, and Gan mice, which express activated prostaglandin E2 and Wnt in the gastric mucosa and develop gastric tumors. We measured expression of epithelial cell-enriched microRNAs and used bioinformatics analyses to integrate data from different systems to identify inflammation-associated microRNAs. We validated our findings in gastric tissues from mice and evaluated protein functions in gastric cell lines (SNU-719, SNU-601, SNU-638, AGS, and GIF-14) and knockout mice. Organoids were cultured from gastric corpus tissues of wild-type and miR-135b–knockout C57BL/6 mice. We measured levels of microRNAs in pairs of gastric tumors and nontumor mucosa from 28 patients in Japan.</P> <P><B>Results</B></P> <P>We found microRNA 135b (miR-135B) to be the most overexpressed microRNA in gastric tissues from K19-C2mE and Gan mice: levels increased during the early stages of gastritis-associated carcinogenesis. Levels of miR-135B were also increased in gastric tumor tissues from <I>gp130</I> <SUP> <I>F/F</I> </SUP> mice and patients compared with nontumor tissues. In gastric organoids and immortalized cell lines, expression of miR-135B was induced by interleukin 1 signaling. K19-C2mE mice with disruption of <I>Mir-135b</I> developed hyperplastic lesions that were 50% smaller than mice without <I>Mir-135b</I> disruption and had significant reductions in cell proliferation. Expression of miR-135B in gastric cancer cell lines increased their colony formation, migration, and sphere formation. We identified <I>FOXN3</I> and <I>RECK</I> messenger RNAs (mRNAs) as targets of miR-135B; their knockdown reduced migration of gastric cancer cell lines. Levels of <I>FOXN3</I> and <I>RECK</I> mRNAs correlated inversely with levels of miR-135B in human gastric tumors and in inflamed mucosa from K19-C2mE mice.</P> <P><B>Conclusions</B></P> <P>We found expression of miR-135B to be up-regulated by interleukin L1 signaling in gastric cancer cells and organoids. miR-135B promotes invasiveness and stem-cell features of gastric cancer cells in culture by reducing <I>FOXN3</I> and <I>RECK</I> messenger RNAs. Levels of these messenger RNA targets, which encode tumor suppressor, are reduced in human gastric tumors.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Changes in the components of salivary exosomes due to initial periodontal therapy
Arisa Yamaguchi,Yuto Tsuruya,Kazuma Igarashi,Zhenyu Jin,Mizuho Yamazaki-Takai,Hideki Takai,Yohei Nakayama,Yorimasa Ogata 대한치주과학회 2023 Journal of Periodontal & Implant Science Vol.53 No.5
Purpose: Exosomes are membrane vesicles that are present in body fluids and contain proteins, lipids, and microRNA (miRNA). Periodontal tissue examinations assess the degree of periodontal tissue destruction according to the probing depth (PD), clinical attachment loss (CAL), bleeding on probing, and X-ray examinations. However, the accurate evaluation of the prognosis of periodontitis is limited. In this study, we collected saliva from patients before and after initial periodontal therapy (IPT) and compared changes in the clinical parameters of periodontitis with changes in the components of salivary exosomes. Methods: Saliva was collected from patients with stage III and IV periodontitis at the first visit and post-IPT. Exosomes were purified from the saliva, and total protein and RNA were extracted. Changes in expression levels of C6, CD81, TSG101, HSP70, and 6 kinds of miRNA were analyzed by western blots and real-time polymerase chain reaction. Results: Patients with increased C6 expression after IPT had significantly higher levels of periodontal inflamed surface area (PISA), miR-142, and miR-144 before and after IPT than patients with decreased C6 expression after IPT. Patients with decreased and unchanged CD81 expression after IPT showed significantly higher PD, CAL, and PISA before IPT than after IPT. Patients with decreased and unchanged TSG101 expression after IPT had significantly higher PD before IPT than after IPT. Patients with increased HSP70 expression after IPT had significantly higher PD and PISA before and after IPT than patients with unchanged HSP70 after IPT. The expression levels of miR-142, miR-144, miR-200b, and miR-223 changed with changes in the levels of C6, CD81, TSG101, and HSP70 in the salivary exosomes of periodontitis patients before and after IPT. Conclusions: The expression levels of proteins and miRNAs in salivary exosomes significantly changed after IPT in periodontitis patients, suggesting that the components of exosomes could serve as biomarkers for periodontitis.
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