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173 results on '"Qin, Xian-Yang"'

1. A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor

Author

Furutani, Yutaka, Hirano, Yoshinori, Toguchi, Mariko, Higuchi, Shoko, Qin, Xian-Yang, Yanaka, Kaori, Sato-Shiozaki, Yumi, Takahashi, Nobuaki, Sakai, Marina, Kongpracha, Pornparn, Suzuki, Takehiro, Dohmae, Naoshi, Kukimoto-Niino, Mutsuko, Shirouzu, Mikako, Nagamori, Shushi, Suzuki, Harukazu, Kobayashi, Kaoru, Masaki, Takahiro, Koyama, Hiroo, Sekiba, Kazuma, Otsuka, Motoyuki, Koike, Kazuhiko, Kohara, Michinori, Kojima, Soichi, Kakeya, Hideaki, and Matsuura, Tomokazu

Published
2023
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3. Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid

Author

Qin, Xian-Yang, Furutani, Yutaka, Yonezawa, Kento, Shimizu, Nobutaka, Kato-Murayama, Miyuki, Shirouzu, Mikako, Xu, Yali, Yamano, Yumiko, Wada, Akimori, Gailhouste, Luc, Shrestha, Rajan, Takahashi, Masataka, Keillor, Jeffrey W., Su, Ting, Yu, Wenkui, Fujii, Shinya, Kagechika, Hiroyuki, Dohmae, Naoshi, Shirakami, Yohei, Shimizu, Masahito, Masaki, Takahiro, Matsuura, Tomokazu, Suzuki, Harukazu, and Kojima, Soichi

Published
2023
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5. Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

Author

Qin, Xian‐Yang, Shirakami, Yohei, Honda, Masao, Yeh, Shiou‐Hwei, Numata, Kazushi, Lai, Ya‐Yun, Li, Chiao‐Ling, Wei, Feifei, Xu, Yali, Imai, Kenji, Takai, Koji, Chuma, Makoto, Komatsu, Nagisa, Furutani, Yutaka, Gailhouste, Luc, Aikata, Hiroshi, Chayama, Kazuaki, Enomoto, Masaru, Tateishi, Ryosuke, and Kawaguchi, Kazunori

Subjects
BIOMARKERS, CLINICAL trials, PROGNOSIS, RETINOIDS, BLOOD proteins, HEPATOCELLULAR carcinoma
Abstract

The proto‐oncogene MYCN expression marked a cancer stem‐like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre‐ and post‐surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non‐cirrhotic or single‐tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long‐term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4‐week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p =.022). In conclusion, serum MYCN holds promise for biomarker‐based precision medicine for the prevention of HCC, long‐term prognosis of early‐stage HCC, and identification of high‐response subgroups for ACR‐based treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid

Author

Qin, Xian-Yang, Suzuki, Harukazu, Honda, Masao, Okada, Hikari, Kaneko, Shuichi, Inoue, Ikuyo, Ebisui, Etsuko, Hashimoto, Kosuke, Carninci, Piero, Kanki, Keita, Tatsukawa, Hideki, Ishibashi, Naoto, Masaki, Takahiro, Matsuura, Tomokazu, Kagechika, Hiroyuki, Toriguchi, Kan, Hatano, Etsuro, Shirakami, Yohei, Shiota, Goshi, Shimizu, Masahito, Moriwaki, Hisataka, and Kojima, Soichi

Published
2018

12. Ratio of creatine/betaine in the liver of mouse DEN-initiated HCC model from Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Author

Qin, Xian-Yang, primary, Tatsukawa, Hideki, primary, Hitomi, Kiyotaka, primary, Shirakami, Yohei, primary, Ishibashi, Naoto, primary, Shimizu, Masahito, primary, Moriwaki, Hisataka, primary, and Kojima, Soichi, primary

Published
2023
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16. Principal metabolic maps of major metabolites illustrated using VANTED from Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

Author

Qin, Xian-Yang, primary, Tatsukawa, Hideki, primary, Hitomi, Kiyotaka, primary, Shirakami, Yohei, primary, Ishibashi, Naoto, primary, Shimizu, Masahito, primary, Moriwaki, Hisataka, primary, and Kojima, Soichi, primary

Published
2023
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19. A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor

Author

00270596, Furutani, Yutaka, Hirano, Yoshinori, Toguchi, Mariko, Higuchi, Shoko, Qin, Xian-Yang, Yanaka, Kaori, Sato-Shiozaki, Yumi, Takahashi, Nobuaki, Sakai, Marina, Kongpracha, Pornparn, Suzuki, Takehiro, Dohmae, Naoshi, Kukimoto-Niino, Mutsuko, Shirouzu, Mikako, Nagamori, Shushi, Suzuki, Harukazu, Kobayashi, Kaoru, Masaki, Takahiro, Koyama, Hiroo, Sekiba, Kazuma, Otsuka, Motoyuki, Koike, Kazuhiko, Kohara, Michinori, Kojima, Soichi, Kakeya, Hideaki, Matsuura, Tomokazu, 00270596, Furutani, Yutaka, Hirano, Yoshinori, Toguchi, Mariko, Higuchi, Shoko, Qin, Xian-Yang, Yanaka, Kaori, Sato-Shiozaki, Yumi, Takahashi, Nobuaki, Sakai, Marina, Kongpracha, Pornparn, Suzuki, Takehiro, Dohmae, Naoshi, Kukimoto-Niino, Mutsuko, Shirouzu, Mikako, Nagamori, Shushi, Suzuki, Harukazu, Kobayashi, Kaoru, Masaki, Takahiro, Koyama, Hiroo, Sekiba, Kazuma, Otsuka, Motoyuki, Koike, Kazuhiko, Kohara, Michinori, Kojima, Soichi, Kakeya, Hideaki, and Matsuura, Tomokazu

Abstract

IFN-alpha have been reported to suppress hepatitis B virus (HBV) cccDNA via APOBEC3 cytidine deaminase activity through interferon signaling. To develop a novel anti-HBV drug for a functional cure, we performed in silico screening of the binding compounds fitting the steric structure of the IFN-alpha-binding pocket in IFNAR2. We identified 37 compounds and named them in silico cccDNA modulator (iCDM)-1–37. We found that iCDM-34, a new small molecule with a pyrazole moiety, showed anti-HCV and anti-HBV activities. We measured the anti-HBV activity of iCDM-34 dependent on or independent of entecavir (ETV). iCDM-34 suppressed HBV DNA, pgRNA, HBsAg, and HBeAg, and also clearly exhibited additive inhibitory effects on the suppression of HBV DNA with ETV. We confirmed metabolic stability of iCDM-34 was stable in human liver microsomal fraction. Furthermore, anti-HBV activity in human hepatocyte-chimeric mice revealed that iCDM-34 was not effective as a single reagent, but when combined with ETV, it suppressed HBV DNA compared to ETV alone. Phosphoproteome and Western blotting analysis showed that iCDM-34 did not activate IFN-signaling. The transcriptome analysis of interferon-stimulated genes revealed no increase in expression, whereas downstream factors of aryl hydrocarbon receptor (AhR) showed increased levels of the expression. CDK1/2 and phospho-SAMHD1 levels decreased under iCDM-34 treatment. In addition, AhR knockdown inhibited anti-HCV activity of iCDM-34 in HCV replicon cells. These results suggest that iCDM-34 decreases the phosphorylation of SAMHD1 through CDK1/2, and suppresses HCV replicon RNA, HBV DNA, and pgRNA formation.

Published
2023

23. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

FANTOM Consortium, Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, J. Kenneth, Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, S. Peter, Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015

32. GENE REGULATION: Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, Kenneth J., Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, Peter S., Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015
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39. MicroRNA‐493‐5p‐mediated repression of theMYCNoncogene inhibits hepatic cancer cell growth and invasion

Author

Yasukawa, Ken, primary, Liew, Lee Chuen, additional, Hagiwara, Keitaro, additional, Hironaka‐Mitsuhashi, Ai, additional, Qin, Xian‐Yang, additional, Furutani, Yutaka, additional, Tanaka, Yasuhito, additional, Nakagama, Hitoshi, additional, Kojima, Soichi, additional, Kato, Takashi, additional, Ochiya, Takahiro, additional, and Gailhouste, Luc, additional

Published
2020
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41. An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes

Author

00270596, Furutani, Yutaka, Toguchi, Mariko, Shiozaki-Sato, Yumi, Qin, Xian-Yang, Ebisui, Etsuko, Higuchi, Shoko, Sudoh, Masayuki, Suzuki, Harukazu, Takahashi, Nobuaki, Watashi, Koichi, Wakita, Takaji, Kakeya, Hideaki, Kojima, Soichi, 00270596, Furutani, Yutaka, Toguchi, Mariko, Shiozaki-Sato, Yumi, Qin, Xian-Yang, Ebisui, Etsuko, Higuchi, Shoko, Sudoh, Masayuki, Suzuki, Harukazu, Takahashi, Nobuaki, Watashi, Koichi, Wakita, Takaji, Kakeya, Hideaki, and Kojima, Soichi

Published
2019

42. An interferon-like small chemical compound CDM-3008 suppresses hepatitis B virus through induction of interferon-stimulated genes

Author

Furutani, Yutaka, primary, Toguchi, Mariko, additional, Shiozaki-Sato, Yumi, additional, Qin, Xian-Yang, additional, Ebisui, Etsuko, additional, Higuchi, Shoko, additional, Sudoh, Masayuki, additional, Suzuki, Harukazu, additional, Takahashi, Nobuaki, additional, Watashi, Koichi, additional, Wakita, Takaji, additional, Kakeya, Hideaki, additional, and Kojima, Soichi, additional

Published
2019
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44. Data Descriptor : FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A., Babina, Magda, Baillie, J. Kenneth, Barnett, Timothy C., Beckhouse, Anthony G., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J., Clevers, Hans C., Davis, Carrie A., Detmar, Michael, Dohi, Taeko, Edge, Albert S. B., Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C., Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley M., Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B., Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J., Hume, David A., Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I., Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Klein, Sarah, Klinken, S. Peter, Knox, Alan J., Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J., Motohashi, Hozumi, Mummery, Christine L., Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sheng, Guojun, Shin, Jay W., Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M., Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G., Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O., Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R. R., Hayashizaki, Yoshihide, Medicum, University of Helsinki, Forensic Medicine, Department of Forensic Medicine, and PaleOmics Laboratory

Subjects
ENHANCERS, MAMMALIAN-CELLS, UCSC GENOME BROWSER, VISUALIZATION, UPDATE, GROWTH, IN-VITRO, TRANSCRIPTION, 3111 Biomedicine, ATLAS, GENE-EXPRESSION
Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

45. MicroRNA‐493‐5p‐mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion.

Author

Yasukawa, Ken, Liew, Lee Chuen, Hagiwara, Keitaro, Hironaka‐Mitsuhashi, Ai, Qin, Xian‐Yang, Furutani, Yutaka, Tanaka, Yasuhito, Nakagama, Hitoshi, Kojima, Soichi, Kato, Takashi, Ochiya, Takahiro, and Gailhouste, Luc

Abstract

Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer‐related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA could critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR‐493‐5p, a major tumor suppressor miRNA that inactivates miR‐483‐3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR‐493‐5p. In particular, the canonical MYCN protooncogene (MYCN) appeared to be an attractive target of miR‐493‐5p given its significant inhibition through 3′‐UTR targeting in miR‐493‐5p‐rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR‐493‐5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anticancer effect of miR‐493‐5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR‐493‐5p activity. In summary, miR‐493‐5p is a pivotal miRNA that modulates various oncogenes after its reexpression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action could provide valuable tools for miRNA replacement therapies. [ABSTRACT FROM AUTHOR]

Published
2020
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46. Prevention of arachidonic acid-induced liver injury by controlling oxidative stress-mediated transglutaminase activation with garlic extracts.

Author

Qin, Xian-Yang, Su, Ting, and Kojima, Soichi

Subjects
*ARACHIDONIC acid, *FATTY liver, *UNSATURATED fatty acids, *LIVER injuries, *GARLIC, *LIVER cells
Abstract

Garlic and its sulfur constituents have numerous biological functions, such as antioxidant, anti-inflammatory, anti-microbial, anticancer, antidiabetic and cardioprotective effects. Fatty liver diseases, such as non-alcoholic steatohepatitis, which is characterized by the accumulation of lipids and oxidative stress in hepatocytes and continual liver damage, has attracted much attention, and it is believed that it will become the leading etiology of liver cancer. We have previously reported that the growth-suppressive effects of arachidonic acid (AA), an unsaturated fatty acid known to be a pro-inflammatory precursor, is accompanied by the production of reactive oxygen species followed by the nuclear accumulation and activation of the protein crosslinking enzyme, transglutaminase (TG)2. In this study, we examined the potential role of garlic extracts in preventing the growth-suppressive effects of AA on human hepatic cells. We also aimed to provide a mechanistic insight regarding the association between the hepatoprotective effects of garlic extract and the inhibition of the TG-related crosslinking of nuclear proteins, which is not associated with hepatic lipid partitioning mediated by stearoyl-CoA desaturase-1. Given the critical roles of unsaturated fatty acids in the regulation of cancer cell stemness and immune surveillance in the context of chronic injury, we propose that garlic extracts may serve as a therapeutic option for the prevention of chronic liver injury and inflammation, as well as for the prevention of the carcinogenesis of fatty livers. [ABSTRACT FROM AUTHOR]

Published
2020
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49. FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A, Babina, Magda, Baillie, J Kenneth, Barnett, Timothy C, Beckhouse, Anthony G, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J, Clevers, Hans C, Davis, Carrie A, Detmar, Michael, Dohi, Taeko, Edge, Albert S B, Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley M, Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B, Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J, Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hume, David A, Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I, Kempfle, Judith S, Kenna, Tony J, Kere, Juha, Khachigian, Levon M, Kitamura, Toshio, Klein, Sarah, Klinken, S Peter, Knox, Alan J, Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-Sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J, Motohashi, Hozumi, Mummery, Christine L, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G, Schwegmann, Anita, Sheng, Guojun, Shin, Jay W, Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M, Verardo, Roberto, Vijayan, Dipti, Wells, Christine A, Winteringham, Louise N, Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G, Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O, Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R R, Hayashizaki, Yoshihide, Noguchi, Shuhei, Arakawa, Takahiro, Fukuda, Shiro, Furuno, Masaaki, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Kaida, Kaoru, Kaiho, Ai, Kanamori-Katayama, Mutsumi, Kawashima, Tsugumi, Kojima, Miki, Kubosaki, Atsutaka, Manabe, Ri-ichiroh, Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakazato, Kenichi, Ninomiya, Noriko, Nishiyori-Sueki, Hiromi, Noma, Shohei, Saijyo, Eri, Saka, Akiko, Sakai, Mizuho, Simon, Christophe, Suzuki, Naoko, Tagami, Michihira, Watanabe, Shoko, Yoshida, Shigehiro, Arner, Peter, Axton, Richard A, Babina, Magda, Baillie, J Kenneth, Barnett, Timothy C, Beckhouse, Anthony G, Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Carlisle, Ailsa J, Clevers, Hans C, Davis, Carrie A, Detmar, Michael, Dohi, Taeko, Edge, Albert S B, Edinger, Matthias, Ehrlund, Anna, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Farach-Carson, Mary C, Faulkner, Geoffrey J, Ferrai, Carmelo, Fisher, Malcolm E, Forrester, Lesley M, Fujita, Rie, Furusawa, Jun-ichi, Geijtenbeek, Teunis B, Gingeras, Thomas, Goldowitz, Daniel, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J, Hamaguchi, Masahide, Hara, Mitsuko, Hasegawa, Yuki, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hume, David A, Ikawa, Tomokatsu, Ishizu, Yuri, Kai, Chieko, Kawamoto, Hiroshi, Kawamura, Yuki I, Kempfle, Judith S, Kenna, Tony J, Kere, Juha, Khachigian, Levon M, Kitamura, Toshio, Klein, Sarah, Klinken, S Peter, Knox, Alan J, Kojima, Soichi, Koseki, Haruhiko, Koyasu, Shigeo, Lee, Weonju, Lennartsson, Andreas, Mackay-Sim, Alan, Mejhert, Niklas, Mizuno, Yosuke, Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Morris, Kelly J, Motohashi, Hozumi, Mummery, Christine L, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Pradhan-Bhatt, Swati, Qin, Xian-Yang, Rehli, Michael, Rizzu, Patrizia, Roy, Sugata, Sajantila, Antti, Sakaguchi, Shimon, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schmidl, Christian, Schneider, Claudio, Schulze-Tanzil, Gundula G, Schwegmann, Anita, Sheng, Guojun, Shin, Jay W, Sugiyama, Daisuke, Sugiyama, Takaaki, Summers, Kim M, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tomoiu, Andru, Toyoda, Hiroo, van de Wetering, Marc, van den Berg, Linda M, Verardo, Roberto, Vijayan, Dipti, Wells, Christine A, Winteringham, Louise N, Wolvetang, Ernst, Yamaguchi, Yoko, Yamamoto, Masayuki, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Yonekura, Yohei, Zhang, Peter G, Zucchelli, Silvia, Abugessaisa, Imad, Arner, Erik, Harshbarger, Jayson, Kondo, Atsushi, Lassmann, Timo, Lizio, Marina, Sahin, Serkan, Sengstag, Thierry, Severin, Jessica, Shimoji, Hisashi, Suzuki, Masanori, Suzuki, Harukazu, Kawai, Jun, Kondo, Naoto, Itoh, Masayoshi, Daub, Carsten O, Kasukawa, Takeya, Kawaji, Hideya, Carninci, Piero, Forrest, Alistair R R, and Hayashizaki, Yoshihide

Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

50. Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes

Author

Qin, Xian-Yang, primary, Hara, Mitsuko, additional, Arner, Erik, additional, Kawaguchi, Yoshikuni, additional, Inoue, Ikuyo, additional, Tatsukawa, Hideki, additional, Furutani, Yutaka, additional, Nagatsuma, Keisuke, additional, Matsuura, Tomokazu, additional, Wei, Feifei, additional, Kikuchi, Jun, additional, Sone, Hideko, additional, Daub, Carsten, additional, Kawaji, Hideya, additional, Lassmann, Timo, additional, Itoh, Masayoshi, additional, Suzuki, Harukazu, additional, Carninci, Piero, additional, Hayashizaki, Yoshihide, additional, Kokudo, Norihiro, additional, Forrest, Alistair R.R., additional, and Kojima, Soichi, additional

Published
2017
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