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Multidisciplinary Sciences
Mitsuo Wada, Kayo Yukawa, Hiroyuki Ogasawara, Koichi Suzawa, Tatsuya Maekawa, Yoshihisa Yamamoto, Takeshi Ohta, Eunyoung Lee, Takashi Miki
Summary: The study revealed that Gpr52-deficient mice showed leanness, reduced liver weight, decreased hepatic de novo lipogenesis, and enhanced insulin sensitivity. The synthetic GPR52 agonist c11 promoted fatty acid biosynthesis, while cholesterol biosynthesis was not affected. Gpr52 was also found to participate in the high-fat diet-induced fatty acid synthesis in the liver.
Article
Endocrinology & Metabolism
Takanori Hayashi, Tetsuya Kubota, Inoue Mariko, Iseki Takamoto, Masakazu Aihara, Yoshitaka Sakurai, Nobuhiro Wada, Takashi Miki, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki
Summary: The study revealed that brain Irs1 plays crucial roles in regulating neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.
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Oncology
Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Kazuya Shimoda, Tomoaki Tanaka, Goro Sashida, Atsushi Iwama
Summary: The insufficiency of PRC1.1, a component of polycomb repressive complex 1, promotes the development of myelofibrosis and acts as a tumor suppressor in this process. This impact is distinct from the effect of PRC2 insufficiency on the pathogenesis of myelofibrosis.
Article
Biochemistry & Molecular Biology
Yoshiro Hirasaki, Atsushi Okabe, Masaki Fukuyo, Bahityar Rahmutulla, Yasunobu Mano, Motoaki Seki, Takayuki Hoshii, Takao Namiki, Atsushi Kaneda
Summary: This study found that cinobufagin can induce apoptosis in human acute myeloid leukaemia cells and has inhibitory effects on c-Myc. Transcriptomic analysis and gene set enrichment analysis further revealed its mechanisms of action.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Oncology
Sawako Suzuki, Divya Venkatesh, Hiroaki Kanda, Akitoshi Nakayama, Hiroyuki Hosokawa, Eunyoung Lee, Takashi Miki, Brent R. Stockwell, Koutaro Yokote, Tomoaki Tanaka, Carol Prives
Summary: This study demonstrates that the key regulator of glutaminolysis, GLS2, can limit HCC in vivo by promoting ferroptosis through aKG-dependent lipid ROS, which in turn might lay the foundation for a novel therapeutic approach.
Article
Biochemistry & Molecular Biology
Yujie Ma, Eunyoung Lee, Hayato Yoshikawa, Tomoe Noda, Junki Miyamoto, Ikuo Kimura, Ryo Hatano, Takashi Miki
Summary: Phloretin suppresses maltose/miglitol-induced GLP-1 secretion through inhibiting SCFAs produced by microbiome. GLUT2 is not essential for glucose/phloridzin-induced GLP-1 secretion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Masayuki Urabe, Keisuke Matsusaka, Tetsuo Ushiku, Masaki Fukuyo, Bahityar Rahmutulla, Hiroharu Yamashita, Yasuyuki Seto, Masashi Fukayama, Atsushi Kaneda
Summary: This study analyzed DNA methylation epigenotypes in adenocarcinomas of the esophagogastric junction (AEG) and non-neoplastic columnar mucosae (NM), and identified four distinct DNA methylation epigenotypes. The results showed that inflammation status determined DNA methylation epigenotypes, and gastric or esophagogastric junction mucosae associated with inflammation displayed lower methylation levels. Additionally, the study found that AEG showed enrichment in high methylation epigenotype (HME) and had a poorer prognosis.
Article
Multidisciplinary Sciences
Masanori Fujimoto, Masataka Yokoyama, Masahiro Kiuchi, Hiroyuki Hosokawa, Akitoshi Nakayama, Naoko Hashimoto, Ikki Sakuma, Hidekazu Nagano, Kazuyuki Yamagata, Fujimi Kudo, Ichiro Manabe, Eunyoung Lee, Ryo Hatano, Atsushi Onodera, Kiyoshi Hirahara, Koutaro Yokote, Takashi Miki, Toshinori Nakayama, Tomoaki Tanaka
Summary: This study reveals the involvement of innate lymphoid cells (ILC2s) in regulating blood glucose levels in the liver through their interaction with specific hepatocytes. The ILC2s suppress gluconeogenesis and maintain glucose homeostasis via Interleukin-13 signaling. The findings provide insights into the important role and molecular mechanism of liver ILC2s in glucose metabolism.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Alimasi Aersilan, Naoko Hashimoto, Kazuyuki Yamagata, Masataka Yokoyama, Akitoshi Nakayama, Xiaoyan Shi, Hidekazu Nagano, Ikki Sakuma, Nijiro Nohata, Takashi Kinoshita, Naohiko Seki, Bahityar Rahmutulla, Atsushi Kaneda, Siti Nurul Zhahara, Yingbo Gong, Motoi Nishimura, Shoichiro Kawauchi, Eiryo Kawakami, Tomoaki Tanaka
Summary: The microRNA miR-874 acts as a potential tumor suppressor by suppressing target genes in various cancer types. This study reveals the relationship between miR-874-induced apoptosis and the mevalonate pathway, as well as its association with the tumor suppressor p53. The findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, leading to the activation of the p53 pathway and promoting cell cycle arrest or apoptosis.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Satoru Kondo, Atsushi Okabe, Takuya Nakagawa, Keisuke Matsusaka, Masaki Fukuyo, Bahityar Rahmutulla, Hirotomo Dochi, Harue Mizokami, Yuki Kitagawa, Tomoya Kurokawa, Masato Mima, Kazuhira Endo, Hisashi Sugimoto, Naohiro Wakisaka, Kiyoshi Misawa, Tomokazu Yoshizaki, Atsushi Kaneda
Summary: Nasopharyngeal carcinoma is a malignancy associated with Epstein-Barr virus and epigenetic abnormalities play important roles in its development. The latent membrane protein 1 (LMP1) is a key factor in inducing aberrant DNA methylation of tumour suppressor genes. This study identified LMP1-inducible methylation genes and demonstrated that DERL3 repression by DNA methylation contributes to the progression of nasopharyngeal carcinoma. The findings suggest potential targets for therapeutic intervention.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Takato Inoue, Kazuaki Matsuda, Keisuke Matsusaka, Masaya Nakajima, Yukari Takeno, Toko Miyazaki, Takahiko Shintaku, Natsumi Yoda, Takahiko Saito, Eriko Ikeda, Yasunobu Mano, Kenichi Shinohara, Bahityar Rahmutulla, Masaki Fukuyo, Kazuko Kita, Tetsuhiro Nemoto, Atsushi Kaneda
Summary: Compounds with 3,4-fused tricyclic indole framework, such as FTI-6D, have cytotoxic effects on various human cancer cell lines. FTI-6D induces apoptosis through activation of the p53 downstream apoptotic pathway and cleavage of caspase-9 and caspase-3. The anti-proliferative effect of FTI-6D is observed in cancer cells with wild-type TP53, but not in cells with mutated TP53.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Cell Biology
Takayuki Hoshii, Sarah Perlee, Sota Kikuchi, Bahityar Rahmutulla, Masaki Fukuyo, Takeshi Masuda, Sumio Ohtsuki, Tomoyoshi Soga, Behnam Nabet, Atsushi Kaneda
Summary: The protein degrader technology was used in this study to degrade SETD1A and investigate its role in acute myeloid leukemia (AML) cells. The results showed that SETD1A degradation led to downregulation of DNA repair and heme biosynthesis pathways, and SETD1A was also found to be essential for maintaining mitochondrial respiration in AML cells. Furthermore, the study revealed a non-enzymatic role of SETD1A in transcriptional pause release, providing insight into the mechanism of RNA polymerase II (RNAPII) pausing and its function in cancer.
Article
Biology
Azusa Yamato, Hidekazu Nagano, Yue Gao, Tatsuma Matsuda, Naoko Hashimoto, Akitoshi Nakayama, Kazuyuki Yamagata, Masataka Yokoyama, Yingbo Gong, Xiaoyan Shi, Siti Nurul Zhahara, Takashi Kono, Yuki Taki, Naoto Furuki, Motoi Nishimura, Kentaro Horiguchi, Yasuo Iwadate, Masaki Fukuyo, Bahityar Rahmutulla, Atsushi Kaneda, Yoshinori Hasegawa, Yusuke Kawashima, Osamu Ohara, Tetsuo Ishikawa, Eiryo Kawakami, Yasuhiro Nakamura, Naoko Inoshita, Shozo Yamada, Noriaki Fukuhara, Hiroshi Nishioka, Tomoaki Tanaka
Summary: This study integrates the genetic alterations, protein expressions, and clinical characteristics of growth hormone-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors to identify molecules associated with acromegaly characteristics. The results reveal a biological connection between GNAS mutations and the clinical and biochemical characteristics of acromegaly, providing potential targets for medical treatment efficacy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah Perlee, Sota Kikuchi, Tomoyoshi Nakadai, Takeshi Masuda, Sumio Ohtsuki, Makoto Matsumoto, Bahityar Rahmutulla, Masaki Fukuyo, Paolo Cifani, Alex Kentsis, Robert G. Roeder, Atsushi Kaneda, Takayuki Hoshii
Summary: The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through the recruitment of cyclin K and regulation of DNA damage response genes. The FLOS domain of SETD1A interacts with mitosis-associated proteins BuGZ/BUB3 and inhibition of both cyclin K and BuGZ/BUB3-binding motifs in SETD1A shows synergistic antileukemic effects. BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions, and their interaction with SETD1A is required for leukemia cell proliferation.
Article
Cell Biology
Yoshinobu Hirano, Takayuki Nakagomi, Akiko Nakano-Doi, Shuji Kubo, Yusuke Minato, Toshinori Sawano, Masafumi Sakagami, Kenzo Tsuzuki
Summary: We have previously shown that neural stem/progenitor cells (NSPCs) are induced in and around areas affected by ischemic stroke in mice. These injury/ischemia-induced NSPCs (iNSPCs) can differentiate into functional neurons in vitro, indicating a self-repair mechanism after injury. However, during the healing process, the ischemic areas are occupied by inflammatory cells, primarily microglial cells/macrophages (MGs/Mfs), and neurogenesis rarely occurs. To investigate the role of MGs/Mfs in regulating iNSPCs, we isolated iNSPCs from the ischemic areas and found that the presence of MGs/Mfs significantly reduces both the proliferation and differentiation of iNSPCs into neuronal cells, thus inhibiting neurogenesis. Depleting MG/Mfs using clodronate encapsulated in liposomes mitigated these effects. Our results suggest that regulating MGs/Mfs is crucial for achieving iNSPC-based neural regeneration after ischemic stroke.