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3. Regular exercise suppresses steatosis‐associated liver cancer development by degrading E2F1 and c‐Myc via circadian gene upregulation.

Author

Huyen, Vu Thuong, Echizen, Kanae, Yamagishi, Ryota, Kumagai, Miho, Nonaka, Yoshiki, Kodama, Takahiro, Ando, Tatsuya, Yano, Megumu, Takada, Naoki, Takasugi, Masaki, Kamachi, Fumitaka, and Ohtani, Naoko

Subjects
LIVER cancer, GENE expression profiling, CARCINOGENESIS, CELL proliferation, CANCER prevention, CIRCADIAN rhythms
Abstract

Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis‐associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non‐exercise groups. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. As circadian rhythm disruption is known to cause various diseases, including cancer, improving circadian rhythm through exercise could contribute to cancer prevention. We further found that the expression of a series of E2F1 and c‐Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercise group. However, the expression of E2F1 and c‐Myc was transcriptionally unchanged but degraded at the post‐translational level by exercise. Cry2, which is regulated by the Skp1‐Cul1‐FBXL3 (SCFFBXL3) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c‐Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development. [ABSTRACT FROM AUTHOR]

Published
2024
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6. DNA methylation networks underlying mammalian traits

Author

Haghani, Amin, primary, Li, Caesar Z., additional, Robeck, Todd R., additional, Zhang, Joshua, additional, Lu, Ake T., additional, Ablaeva, Julia, additional, Acosta-Rodríguez, Victoria A., additional, Adams, Danielle M., additional, Alagaili, Abdulaziz N., additional, Almunia, Javier, additional, Aloysius, Ajoy, additional, Amor, Nabil M.S., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Banks, Gareth, additional, Belov, Katherine, additional, Bennett, Nigel C., additional, Black, Peter, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Carter, Gerald, additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chakrabarti, Lisa, additional, Chatzistamou, Ioulia, additional, Chavez, Andreas S., additional, Chen, Hao, additional, Cheng, Kaiyang, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, Cook, Joseph A., additional, Cooper, Lisa N., additional, Cossette, Marie-Laurence, additional, Day, Joanna, additional, DeYoung, Joseph, additional, Dirocco, Stacy, additional, Dold, Christopher, additional, Dunnum, Jonathan L., additional, Ehmke, Erin E., additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Erbay, Ebru, additional, Erlacher-Reid, Claire, additional, Faulkes, Chris G., additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gerber, Livia, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Grant, Matthew J, additional, Green, Carla B., additional, Hanson, M. Bradley, additional, Hart, Daniel W., additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Huang, Taosheng, additional, Izpisua Belmonte, Juan Carlos, additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Krützen, Michael, additional, Kwon, Soo Bin, additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaître, Jean-François, additional, Levine, Andrew J., additional, Li, Xinmin, additional, Li, Cun, additional, Lim, Andrea R., additional, Lin, David T. S., additional, Lindemann, Dana M., additional, Liphardt, Schuyler W., additional, Little, Thomas J., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, McClure, Matthew, additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Munshi-South, Jason, additional, Murphy, William J., additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Nyamsuren, Batsaikhan, additional, O’Brien, Justine K., additional, Ginn, Perrie O’Tierney, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Osborn, Steve, additional, Ostrander, Elaine A., additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pedersen, Amy B., additional, Pellegrini, Matteo, additional, Peters, Katharina J., additional, Petersen, Jessica L., additional, Pietersen, Darren W., additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Poganik, Jesse R., additional, Prado, Natalia A., additional, Reddy, Pradeep, additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schmitt, Todd, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shafer, Aaron B.A., additional, Shindyapina, Anastasia V., additional, Simmons, Melanie, additional, Singh, Kavita, additional, Sinha, Ishani, additional, Slone, Jesse, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Staggs, Lydia, additional, Stedman, Nancy, additional, Steinman, Karen J., additional, Stewart, Donald T, additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takahashi, Joseph S., additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Thompson, Michael J., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Villar, Diego, additional, Vinters, Harry V., additional, Vu, Ha, additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yan, Qi, additional, Yao, Mingjia, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Yang, additional, Zhao, Peng, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Gorbunova, Vera, additional, Yang, X. William, additional, Raj, Ken, additional, and Horvath, Steve, additional

Published
2023
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14. Gasdermin D–mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma

Author

Yamagishi, Ryota, primary, Kamachi, Fumitaka, additional, Nakamura, Masaru, additional, Yamazaki, Shota, additional, Kamiya, Tomonori, additional, Takasugi, Masaki, additional, Cheng, Yi, additional, Nonaka, Yoshiki, additional, Yukawa-Muto, Yoshimi, additional, Thuy, Le Thi Thanh, additional, Harada, Yohsuke, additional, Arai, Tatsuya, additional, Loo, Tze Mun, additional, Yoshimoto, Shin, additional, Ando, Tatsuya, additional, Nakajima, Masahiro, additional, Taguchi, Hayao, additional, Ishikawa, Takamasa, additional, Akiba, Hisaya, additional, Miyake, Sachiko, additional, Kubo, Masato, additional, Iwakura, Yoichiro, additional, Fukuda, Shinji, additional, Chen, Wei-Yu, additional, Kawada, Norifumi, additional, Rudensky, Alexander, additional, Nakae, Susumu, additional, Hara, Eiji, additional, and Ohtani, Naoko, additional

Published
2022
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18. Galectin-3 promotes the adipogenic differentiation of PDGFRα+ cells and ectopic fat formation in regenerating muscle

Author

Takada, Naoki, primary, Takasugi, Masaki, additional, Nonaka, Yoshiki, additional, Kamiya, Tomonori, additional, Takemura, Kazuaki, additional, Satoh, Junko, additional, Ito, Shinji, additional, Fujimoto, Kosuke, additional, Uematsu, Satoshi, additional, Yoshida, Kayo, additional, Morita, Takashi, additional, Nakamura, Hiroaki, additional, Uezumi, Akiyoshi, additional, and Ohtani, Naoko, additional

Published
2022
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19. The role of cellular senescence and SASP in tumour microenvironment.

Author

Takasugi, Masaki, Yoshida, Yuya, Hara, Eiji, and Ohtani, Naoko

Subjects
*CELLULAR aging, *TUMOR microenvironment, *INHIBITION of cellular proliferation, *CELL cycle, *CANCER treatment
Abstract

Cellular senescence refers to a state of irreversible cell cycle arrest that can be induced by various cellular stresses and is known to play a pivotal role in tumour suppression. While senescence‐associated growth arrest can inhibit the proliferation of cancer‐prone cells, the altered secretory profile of senescent cells, termed the senescence‐associated secretory phenotype, can contribute to the microenvironment that promotes tumour development. Although the senescence‐associated secretory phenotype and its effects on tumorigenesis are both highly context dependent, mechanisms underlying such diversity are becoming better understood, thereby allowing the creation of new strategies to effectively target the senescence‐associated secretory phenotype and senescent cells for cancer therapy. In this review, we discuss the current knowledge on cellular senescence and the senescence‐associated secretory phenotype to develop a structural understanding of their roles in the tumour microenvironment and provide perspectives for future research, including the possibility of senotherapy for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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20. DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders

Author

Horvath, Steve, primary, Haghani, Amin, additional, Macoretta, Nicholas, additional, Ablaeva, Julia, additional, Zoller, Joseph A., additional, Li, Caesar Z., additional, Zhang, Joshua, additional, Takasugi, Masaki, additional, Zhao, Yang, additional, Rydkina, Elena, additional, Zhang, Zhihui, additional, Emmrich, Stephan, additional, Raj, Ken, additional, Seluanov, Andrei, additional, Faulkes, Chris G., additional, and Gorbunova, Vera, additional

Published
2021
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21. Naked Mole-Rat Hematopoietic Stem and Progenitors are Highly Quiescent with an Inherent Myeloid Bias

Author

Emmrich, Stephan, primary, Trapp, Alexandre, additional, Zakusilo, Frances Tolibzoda, additional, Mariotti, Marco, additional, Straight, Maggie E., additional, Zhang, Zhihui, additional, Gray, Spencer, additional, Drage, Michael G., additional, Ke, Zhonghe, additional, Takasugi, Masaki, additional, Klusmann, Jan-Henning, additional, Gladyshev, Vadim N., additional, Seluanov, Andrei, additional, and Gorbunova, Vera, additional

Published
2021
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22. Epigenetic predictors of maximum lifespan and other life history traits in mammals

Author

Li, Caesar Z., primary, Haghani, Amin, additional, Robeck, Todd R., additional, Villar, Diego, additional, Lu, Ake T., additional, Zhang, Joshua, additional, Faulkes, Chris G., additional, Vu, Ha, additional, Ablaeva, Julia, additional, Adams, Danielle M., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Belov, Katherine, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chatzistamou, Ioulia, additional, Chen, Hao, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, DeYoung, Joseph, additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Hanson, M. Bradley, additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaitre, Jean-Francois, additional, Levine, Andrew J., additional, Li, Cun, additional, Li, Xinmin, additional, Lin, David TS, additional, Lindemann, Dana M., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Ostrander, Elaine A., additional, O'Tierney Ginn, Perrie, additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pellegrini, Matteo, additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Prado, Natalia A., additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shindyapina, Anastasia V., additional, Singh, Kavita, additional, Sinha, Ishani, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Steinman, Karen J., additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Vinters, Harry V., additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yang, X. William, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Peng, additional, Zhao, Yang, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Raj, Ken, additional, Gorbunova, Vera, additional, and Horvath, Steve, additional

Published
2021
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23. DNA methylation clocks show slower progression of aging in naked mole-rat queens

Author

Horvath, Steve, primary, Haghani, Amin, additional, Macoretta, Nicholas, additional, Ablaeva, Julia, additional, Zoller, Joseph A., additional, Li, Caesar Z., additional, Zhang, Joshua, additional, Takasugi, Masaki, additional, Zhao, Yang, additional, Rydkina, Elena, additional, Zhang, Zhihui, additional, Emmrich, Stephan, additional, Raj, Ken, additional, Seluanov, Andrei, additional, Faulkes, Chris G., additional, and Gorbunova, Vera, additional

Published
2021
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26. SIRT6 mono-ADP ribosylates KDM2A to locally increase H3K36me2 at DNA damage sites to inhibit transcription and promote repair

Author

Rezazadeh, Sarallah, primary, Yang, David, additional, Biashad, Seyed Ali, additional, Firsanov, Denis, additional, Takasugi, Masaki, additional, Gilbert, Michael, additional, Tombline, Gregory, additional, Bhanu, Natarajan V., additional, Garcia, Benjamin A., additional, Seluanov, Andrei, additional, and Gorbunova, Vera, additional

Published
2020
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28. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

Author

Takasugi Masaki, Yagi Shintaro, Hirabayashi Keiji, and Shiota Kunio

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA), and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes) has not been comprehensively analyzed. Results We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs). These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain. Conclusions A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.

Published
2010
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33. Ablation of the p16INK4a tumour suppressor reverses ageing phenotypes of klotho mice

Author

Sato, Seidai, primary, Kawamata, Yuka, additional, Takahashi, Akiko, additional, Imai, Yoshinori, additional, Hanyu, Aki, additional, Okuma, Atsushi, additional, Takasugi, Masaki, additional, Yamakoshi, Kimi, additional, Sorimachi, Hiroyuki, additional, Kanda, Hiroaki, additional, Ishikawa, Yuichi, additional, Sone, Saburo, additional, Nishioka, Yasuhiko, additional, Ohtani, Naoko, additional, and Hara, Eiji, additional

Published
2015
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