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3. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression

Author

Okada, Nobuhiro, Lin, Chao-Po, Ribeiro, Marcelo C, Biton, Anne, Lai, Gregory, He, Xingyue, Bu, Pengcheng, Vogel, Hannes, Jablons, David M, Keller, Andreas C, Wilkinson, J Erby, He, Biao, Speed, Terry P, and He, Lin

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Lung, Cancer, Genetics, Lung Cancer, Biotechnology, 2.1 Biological and endogenous factors, Adenocarcinoma, Adenocarcinoma of Lung, Animals, Cell Line, Tumor, Feedback, Physiological, Gene Deletion, Gene Expression Regulation, Neoplastic, Haploinsufficiency, Humans, Lung Neoplasms, Mice, MicroRNAs, Proto-Oncogene Proteins, Tumor Cells, Cultured, Tumor Suppressor Protein p53, ras Proteins, miR-34, microRNAs, p53, Mdm4, HDM4, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3' untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop.

Published
2014

4. Application of Na2CO3 as a Sacrificial Electrode Additive in Na‐ion Batteries to Compensate for the Sodium Deficiency in Na2/3[Fe1/2Mn1/2]O2.

Author

Matsuzaki, Masayoshi, Tatara, Ryoichi, Kubota, Kei, Kuroki, Kazutoshi, Hosaka, Tomooki, Umetsu, Kazuteru, Okada, Nobuhiro, and Komaba, Shinichi

Subjects
NEGATIVE electrode, ELECTRIC batteries, PROCESS capability, TRANSITION metal oxides, ELECTRODES, ETHYLENE carbonates
Abstract

Owing to their high discharge capacities, P2‐type transition metal layered oxides have attracted attention for use as positive electrode materials in Na‐ion batteries. However, owing to the Na‐deficient compositions of these oxides, additional Na+ must be supplied using a Na‐metal negative electrode to attain a high capacity in a half‐cell configuration. In this study, solid Na2CO3 powder was introduced into the P2−Na2/3Fe1/2Mn1/2O2 composite positive electrode as a sacrificial salt to compensate for the Na deficiency. Na+ was supplied through the electrochemical oxidative decomposition of Na2CO3 during the initial charging process; the decomposition mechanism responsible for this process was investigated in detail. Online electrochemical mass spectrometry confirmed that Na2CO3 was oxidatively decomposed in combination with the decomposition of the ethylene carbonate electrolyte. This reaction produced CO2, wherein the carbon source was derived from both Na2CO3 and the electrolyte. Consequently, Na+ supplementation improved the reversible capacity of the Na‐ion full cell. This study offers practical insights and a mechanistic understanding of the pre‐doping technique for Na‐free negative electrodes. This approach also compensates for the irreversible reductive capacity in a process that can be easily applied to practical sodium‐ and lithium‐ion batteries and capacitors. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Supplementary Figures from Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion

Author

Li, Fengkai, primary, Kitajima, Shunsuke, primary, Kohno, Susumu, primary, Yoshida, Akiyo, primary, Tange, Shoichiro, primary, Sasaki, Soichiro, primary, Okada, Nobuhiro, primary, Nishimoto, Yuuki, primary, Muranaka, Hayato, primary, Nagatani, Naoko, primary, Suzuki, Misa, primary, Masuda, Sayuri, primary, Thai, Tran C., primary, Nishiuchi, Takumi, primary, Tanaka, Tomoaki, primary, Barbie, David A., primary, Mukaida, Naofumi, primary, and Takahashi, Chiaki, primary

Published
2023
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9. Data from Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion

Author

Li, Fengkai, primary, Kitajima, Shunsuke, primary, Kohno, Susumu, primary, Yoshida, Akiyo, primary, Tange, Shoichiro, primary, Sasaki, Soichiro, primary, Okada, Nobuhiro, primary, Nishimoto, Yuuki, primary, Muranaka, Hayato, primary, Nagatani, Naoko, primary, Suzuki, Misa, primary, Masuda, Sayuri, primary, Thai, Tran C., primary, Nishiuchi, Takumi, primary, Tanaka, Tomoaki, primary, Barbie, David A., primary, Mukaida, Naofumi, primary, and Takahashi, Chiaki, primary

Published
2023
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10. Supplementary Table 2 from Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion

Author

Li, Fengkai, primary, Kitajima, Shunsuke, primary, Kohno, Susumu, primary, Yoshida, Akiyo, primary, Tange, Shoichiro, primary, Sasaki, Soichiro, primary, Okada, Nobuhiro, primary, Nishimoto, Yuuki, primary, Muranaka, Hayato, primary, Nagatani, Naoko, primary, Suzuki, Misa, primary, Masuda, Sayuri, primary, Thai, Tran C., primary, Nishiuchi, Takumi, primary, Tanaka, Tomoaki, primary, Barbie, David A., primary, Mukaida, Naofumi, primary, and Takahashi, Chiaki, primary

Published
2023
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11. Supplementary Table 1 from Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion

Author

Li, Fengkai, primary, Kitajima, Shunsuke, primary, Kohno, Susumu, primary, Yoshida, Akiyo, primary, Tange, Shoichiro, primary, Sasaki, Soichiro, primary, Okada, Nobuhiro, primary, Nishimoto, Yuuki, primary, Muranaka, Hayato, primary, Nagatani, Naoko, primary, Suzuki, Misa, primary, Masuda, Sayuri, primary, Thai, Tran C., primary, Nishiuchi, Takumi, primary, Tanaka, Tomoaki, primary, Barbie, David A., primary, Mukaida, Naofumi, primary, and Takahashi, Chiaki, primary

Published
2023
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12. NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism

Author

Okada, Nobuhiro, Ueki, Chihiro, Shimazaki, Masahiro, Tsujimoto, Goki, Kohno, Susumu, Muranaka, Hayato, Yoshikawa, Kiyotsugu, Takahashi, Chiaki, Okada, Nobuhiro, Ueki, Chihiro, Shimazaki, Masahiro, Tsujimoto, Goki, Kohno, Susumu, Muranaka, Hayato, Yoshikawa, Kiyotsugu, and Takahashi, Chiaki

Abstract

Two splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC.

Published
2023

17. NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression

Author

Tsujimoto, Goki, Ito, Rin, Yoshikawa, Kei, Ueki, Chihiro, Okada, Nobuhiro, Tsujimoto, Goki, Ito, Rin, Yoshikawa, Kei, Ueki, Chihiro, and Okada, Nobuhiro

Abstract

Reprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC.

Published
2022

20. Upregulated CCL20 and CCR6 in Cancer Stem Cells Converted from Mouse iPS Cells

Author

Du, Juan, Seno, Akimasa, Sasada, Saki, Xu, Yanning, Oo, Aung Ko Ko, Hassan, Ghmkin, Ueno, Shunsuke, Afify, Said M., Zahra, Maram H, Okada, Nobuhiro, Chen, Ling, Fu, Xiaoying, Tokutaka, Heizo, Yan, Ting, and Seno, Masaharu

Subjects
CSCs, chemical and pharmacologic phenomena, hemic and immune systems, miPSCs, CCR6, CCL20
Abstract

Background: Cancer stem cells (CSCs) as a class of malignant cancer cells play an important role in tumor progression. Previous studies by our group have demonstrated the establishment of the model of CSCs converting mouse iPS cells (miPSCs) into CSCs by treating the miPSCs with a conditioned medium (CM) of Lewis Lung Carcinoma (LLC) cells with or without the nonmutagenic chemical compounds. CSCs converted from miPSCs developed highly malignant adenocarcinoma when subcutaneously transplanted into the nude mice. Methods: The miPSCs were treated with each compound for 1 week in the presence of a CM of LLC cells. We evaluated the gene expression in the resultant CSCs comparing that in miPSCs by microarray analysis. And the expression of chemokine (C-C motif) ligand 20 (CCL20) and C-C chemokine receptor type 6 (CCR6) in converted cells were evaluated by rt-qPCR. The CCR6 expression in converted cells and primary cells were determined by flow cytometry. Results: As the result, the expression of CCL20 was found upregulated in the presence of CM supplemented with PD0325901. Then we assessed the expression of CCR6, which was considered to be stimulated by CCL20. Then the expression of CCR6 was also found up-regulated. Interestingly, IL17A expression was also observed only in the CSCs from the primary tumor implying the effect of tumor microenvironment. Moreover, significantly high level of CCR6 was showed in flow cytometric analysis. Conclusion: These results suggest that a model of CSCs with CCL20-CCR6 autocrine loop was obtained as the result of the conversion of iPSCs. This CSC should be a good model to study targeting CCR6 as a G protein-coupled receptor (GPCR).

Published
2020

24. Treatment of Retinoblastoma 1–Intact Hepatocellular Carcinoma With Cyclin‐Dependent Kinase 4/6 Inhibitor Combination Therapy

Author

Sheng, Jindan, primary, Kohno, Susumu, additional, Okada, Nobuhiro, additional, Okahashi, Nobuyuki, additional, Teranishi, Kana, additional, Matsuda, Fumio, additional, Shimizu, Hiroshi, additional, Linn, Paing, additional, Nagatani, Naoko, additional, Yamamura, Minako, additional, Harada, Kenichi, additional, Horike, Shin‐ichi, additional, Inoue, Hiroshi, additional, Yano, Seiji, additional, Kumar, Sharad, additional, Kitajima, Shunsuke, additional, Ajioka, Itsuki, additional, and Takahashi, Chiaki, additional

Published
2021
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28. Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Author

Hassan, Ghmkin, primary, Afify, Said M., additional, Nair, Neha, additional, Kumon, Kazuki, additional, Osman, Amira, additional, Du, Juan, additional, Mansour, Hager, additional, Abu Quora, Hagar A, additional, Nawara, Hend M, additional, Satoh, Ayano, additional, Zahra, Maram H., additional, Okada, Nobuhiro, additional, Seno, Akimasa, additional, and Seno, Masaharu, additional

Published
2019
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30. Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion

Author

Li, Fengkai, primary, Kitajima, Shunsuke, additional, Kohno, Susumu, additional, Yoshida, Akiyo, additional, Tange, Shoichiro, additional, Sasaki, Soichiro, additional, Okada, Nobuhiro, additional, Nishimoto, Yuuki, additional, Muranaka, Hayato, additional, Nagatani, Naoko, additional, Suzuki, Misa, additional, Masuda, Sayuri, additional, Thai, Tran C., additional, Nishiuchi, Takumi, additional, Tanaka, Tomoaki, additional, Barbie, David A., additional, Mukaida, Naofumi, additional, and Takahashi, Chiaki, additional

Published
2019
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31. Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

Author

Khayrani, Apriliana Cahya, primary, Mahmud, Hafizah, additional, Oo, Aung Ko Ko, additional, Zahra, Maram H., additional, Oze, Miharu, additional, Du, Juan, additional, Alam, Md Jahangir, additional, Afify, Said M., additional, Quora, Hagar A. Abu, additional, Shigehiro, Tsukasa, additional, Calle, Anna Sanchez, additional, Okada, Nobuhiro, additional, Seno, Akimasa, additional, Fujita, Koki, additional, Hamada, Hiroki, additional, Seno, Yuhki, additional, Mandai, Tadakatsu, additional, and Seno, Masaharu, additional

Published
2019
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38. Passivation of active recombination centers in ZnO by hydrogen doping.

Author

Ohashi, Naoki, Ishigaki, Takamasa, Okada, Nobuhiro, Taguchi, Hiroyuki, Sakaguchi, Isao, Hishita, Shunichi, Sekiguchi, Takashi, and Haneda, Hajime

Subjects
HYDROGEN, LUMINESCENCE, INDUCTIVELY coupled plasma spectrometry, IRRADIATION
Abstract

The effect of hydrogen doping on luminescence properties of ZnO was investigated. Hydrogen was incorporated in the ZnO crystal by irradiation with an inductively coupled plasma (ICP), in particular, the pulse modulated mode operation of ICP, and the luminescence spectra and hydrogen concentration of the resultant samples were analyzed. A hydrogenated region of 20-100 nm was formed at the sample surface by the irradiation and the concentration of hydrogen was 10[SUP17] - 10[SUP18] cm[SUP-3]. Hydrogen doping improved the ultraviolet emission efficiency of all the samples, and the degree of improvement depended on the initial state (impurity concentration) of the original samples. The most significant improvements were recorded for the sample lightly contaminated with Cu, Al, and Li. The correlation between impurity concentration and hydrogen doping effects is discussed from the viewpoint of charge transfer between hydrogen and the other impurities. [ABSTRACT FROM AUTHOR]

Published
2003
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40. Numerical Analysis for Corrosion near Shear Cut Edge of Galvanic Steel Sheet

Author

Fujimoto Shinji, Okada Nobuhiro, Kimoto Masanari, Matsumoto Masamitsu, Kudo Takeo, and Nishihara Katsuhiro

Subjects
Materials science, Chemical substance, Numerical analysis, Metallurgy, Metals and Alloys, Condensed Matter Physics, Corrosion, Ion, Shear (sheet metal), Galvanic corrosion, Materials Chemistry, Galvanic cell, Seawater, Physical and Theoretical Chemistry
Abstract

We have developed a new mathematical model for galvanic corrosion with ions movement, reactions and electroneutrality. In this model, ion density distribution is corrected by solving Poisson's equation to satisfy electroneutrality. Major ion species and reactions are considered in NaCl solution, MgCl2 solution and artificial sea water on a Fe/Zn galvanic couple.Distribution of corrosion products in NaCl solution and MgCl2 solution obtained by numerical analysis agreed well with measured by FTIR method qualitatively.Corrosion progresses at shear cut edge of galvanic steel sheet in NaCl solution, MgCl2 solution and artificial sea water were simulated and discussed. In addition, galvanic corrosion under a paint film near the shear cut edge was computed. The numerical analysis result indicated that concentration of Cl− under the paint film was increased by more than factor of 10.

Published
2011

41. Collision Avoidance for a Visuo-motor System Using Multiple Self-organizing Maps

Author

Han, Min, Okada, Nobuhiro, and Kondo, Eiji

Subjects
Computer Science::Robotics, Self-organizing maps, Visuo-motor system, Collision avoidance, Redundant manipulator, Path planning
Abstract

Collision avoidance for a visuo-motor system in unstructured and cluttered environment is described. The achievement of collision avoidance is based on a simplified path planning system and motion control performed by self-organizing maps. The self-organizing maps are learned to determine joint angles of a redundant manipulator. Since the learning algorithm promises to make the manipulator reach targets precisely with obstacle-free poses, the path planning system only needs to plan a collision-free path for the end effector of the manipulator in the image spaces. By means of the cooperation of two self-organizing maps, the system solves occlusion problems successfully. Simulation results are presented to demonstrate the effectiveness of the proposed approach.

Published
2005

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