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Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells

Experimental and Clinical Endocrinology & Diabetes 2021年第8期130卷 498-508页

作者： Han Yan Zhenzhen Chen Haizeng Zhang Weili Yang Xiangyang Liu Yuhong Meng Rui Xiang Zhe Wu Jingjing Ye Yujing Chi Jichun Yang Department of Physiology and Pathophysiology School of Basic Medical Sciences Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education Center for Non-coding RNA Medicine Peking University Health Science Center Beijing 100191 China Hypertension Center Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Cardiovascular Disease National Center for Cardiovascular Diseases Beijing 100037 China Beijing Key Laboratory of diabetes Research and Care Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Gastroenterology Peking University People’s Hospital Beijing 100044 China Department of Central Laboratory & Institute of Clinical Molecular Biology Peking University People’s Hospital Beijing 100044 China

FAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using sirna transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice.

关键词： FAM3A pancreatic β cells intracellular ATP PDX1 insulin secretion

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Correction to: Preserving or peeling the inferior mesenteric arterial sheath during laparoscopic rectal cancer surgery: a prospective study of surgical outcomes

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BMC surgery 2023年第1期23卷 243页

作者： Qian Li Ye Wang Jia-Wei Wang Long Qian Song Wang Ting-Ting Cao Ya-Bin Xia Xiao-Xu Huang Li Xu Department of Gastrointestinal Surgery First Affiliated Hospital of Wannan Medical College Yijishan Hospital of Wannan Medical College No. 2 Zheshan West Road Wuhu Anhui 241001 China. Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution Wuhu Anhui China. Non-coding RNA Research Center of Wannan Medical College Yijishan Hospital Wuhu Anhui China. Department of Gastrointestinal Surgery First Affiliated Hospital of Wannan Medical College Yijishan Hospital of Wannan Medical College No. 2 Zheshan West Road Wuhu Anhui 241001 China. xiaoxuhuang1984@***. Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution Wuhu Anhui China. xiaoxuhuang1984@***. Non-coding RNA Research Center of Wannan Medical College Yijishan Hospital Wuhu Anhui China. xiaoxuhuang1984@***.

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Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types

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NATURE COMMUNICATIONS 2016年第1期7卷 10499-10510页

作者： Wang, Cheng Gu, Yayun Zhang, Kai Xie, Kaipeng Zhu, Meng Dai, Ningbin Jiang, Yue Guo, Xuejiang Liu, Mingxi Dai, Juncheng Wu, Linxiang Jin, Guangfu Ma, Hongxia Jiang, Tao Yin, Rong Xia, Yankai Liu, Li Wang, Shouyu Shen, Bin Huo, Ran Wang, Qianghu Xu, Lin Yang, Liuqing Huang, Xingxu Shen, Hongbing Sha, Jiahao Hu, Zhibin Nanjing Med Univ State Key Lab Reprod Med Nanjing 210029 Jiangsu Peoples R China Nanjing Med Univ Sch Publ HlthDept Epidemol & Biostat Collaborat Innovat Ctr Canc Personalized Med Jiangsu Key Lab Canc Biomarkers Prevent & Treatme Nanjing 210029 Jiangsu Peoples R China Nanjing Med Univ Sch Basic Med Sci Dept Bioinformat Nanjing 210029 Jiangsu Peoples R China Nanjing Med Univ Affiliated Canc Hosp Collaborat Innovat Ctr Canc Personalized Med Jiangsu Key Lab Mol & Translat Canc Res Nanjing 210009 Jiangsu Peoples R China Nanjing Med Univ Sch Publ HlthDept Mol Cell Biol & Toxicol Collaborat Innovat Ctr Canc Personalized Med Jiangsu Key Lab Canc Biomarkers Prevent & Treatme Nanjing 210029 Jiangsu Peoples R China Nanjing Med Univ Affiliated Hosp 1 Digest Endoscopy Ctr Nanjing 210029 Jiangsu Peoples R China Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Canc Biol Program Dept Mol & Cellular Oncol Houston TX 77030 USA Shanghai Tech Univ Sch Life Sci & Technol Pudong New Area 100 Haike Rd Shanghai 201210 Peoples R China

Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CTgenes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding rnas (namely, CT-ncrnas) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncrna have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies.

关键词： Cancer epigenetics Cancer therapy

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Comprehensive Genomic Characterization of Long non-coding rnas across Human Cancers

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CANCER CELL 2015年第4期28卷 529-540页

作者： Yan, Xiaohui Hu, Zhongyi Feng, Yi Hu, Xiaowen Yuan, Jiao Zhao, Sihai D. Zhang, Youyou Yang, Lu Shan, Weiwei He, Qun Fan, Lingling Kandalaft, Lana E. Tanyi, Janos L. Li, Chunsheng Yuan, Chao-Xing Zhang, Dongmei Yuan, Huiqing Hua, Keqin Lu, Yiling Katsaros, Dionyssios Huang, Qihong Montone, Kathleen Fan, Yi Coukos, George Boyd, Jeff Sood, Anil K. Rebbeck, Timothy Mills, Gordon B. Dang, Chi V. Zhang, Lin Univ Penn Perelman Sch Med Ctr Res Reprod & Womens Hlth Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Abramson Family Canc Res Inst Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Obstet & Gynecol Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Pharmacol Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Pathol & Lab Med Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Radiat Oncol Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Epidemiol & Biostat Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Dept Med Philadelphia PA 19104 USA Fudan Univ Obstet & Gynecol Hosp Shanghai Key Lab Female Reprod Endocrine Related Shanghai 200011 Peoples R China Univ Illinois Dept Stat Champaign IL 61820 USA Shandong Univ Sch Med Dept Biochem & Mol Biol Jinan 250012 Peoples R China Sichuan Univ West China Med Sch Chengdu 610041 Peoples R China Univ Citta Salute Azienda Osped Dept Surg Sci Gynecol Oncol I-10126 Turin Italy Wistar Inst Anat & Biol Philadelphia PA 19104 USA Univ Lausanne Ludwig Ctr Canc Res CH-1007 Lausanne Switzerland Univ Lausanne Dept Oncol CH-1007 Lausanne Switzerland Fox Chase Canc Ctr Canc Genome Inst Philadelphia PA 19111 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77054 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77054 USA Univ Texas MD Anderson Canc Ctr Dept Syst Biol Houston TX 77054 USA

The discovery of long non-coding rna (lncrna) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of lncrna alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atlas. Our results suggest that the expression and dysregulation of lncrnas are highly cancer type specific compared with protein- coding genes. Using the integrative data generated by this analysis, we present a clinically guided small interfering rna screening strategy and a co-expression analysis approach to identify cancer driver lncrnas and predict their functions. This provides a resource for investigating lncrnas in cancer and lays the groundwork for the development of new diagnostics and treatments.

关键词： Cell Line, Tumor Computational Biology/methods Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Genetic Variation Genome, Human Humans Neoplasms/genetics rna, Long noncoding/genetics Transcription, Genetic

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Targeting 17q23 amplicon to overcome the resistance to anti-HER2 therapy in HER2+breast cancer

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NATURE COMMUNICATIONS 2018年第1期9卷 1页

作者： Liu, Yunhua Xu, Jiangsheng Choi, Hyun Ho Han, Cecil Fang, Yuanzhang Li, Yujing Van der Jeught, Kevin Xu, Hanchen Zhang, Lu Frieden, Michael Wang, Lifei Eyvani, Haniyeh Sun, Yifan Zhao, Gang Zhang, Yuntian Liu, Sheng Wan, Jun Huang, Cheng Ji, Guang Lu, Xiongbin He, Xiaoming Zhang, Xinna Indiana Univ Sch Med Dept Med & Mol Genet Indianapolis IN 46202 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Shanghai Univ Tradit Chinese Med Longhua Hosp Inst Digest Dis Shanghai 200032 Peoples R China Ohio State Univ Dept Biomed Engn Columbus OH 43210 USA Ohio State Univ Comprehens Canc Ctr Columbus OH 43210 USA Univ Maryland Fischell Dept Bioengn College Pk MD 20742 USA Univ Sci & Technol China Sch Informat Sci & Technol Dept Elect Sci & Technol Hefei 230027 Anhui Peoples R China Shanghai Univ Tradit Chinese Med Sch Pharm Drug Discovery Lab Shanghai 201203 Peoples R China Indiana Univ Sch Med Indiana Univ Melvin & Bren Simon Canc Ctr Indianapolis IN 46202 USA Univ Maryland Robert E Fischell Inst Biomed Devices College Pk MD 20742 USA Univ Maryland Marlene & Stewart Greenebaum Comprehens Canc Ctr Baltimore MD 21201 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77030 USA

Chromosome 17q23 amplification occurs in similar to 11% of human breast cancers. Enriched in HER2+ breast cancers, the 17q23 amplification is significantly correlated with poor clinical outcomes. In addition to the previously identified oncogene WIP1, we uncover an oncogenic microrna gene, MIR21, in a majority of the WIP1-containing 17q23 amplicons. The 17q23 amplification results in aberrant expression of WIP1 and miR-21, which not only promotes breast tumorigenesis, but also leads to resistance to anti-HER2 therapies. Inhibiting WIP1 and miR-21 selectively inhibits the proliferation, survival and tumorigenic potential of the HER2+ breast cancer cells harboring 17q23 amplification. To overcome the resistance of trastuzumab-based therapies in vivo, we develop pH-sensitive nanoparticles for specific co-delivery of the WIP1 and miR-21 inhibitors into HER2+ breast tumors, leading to a profound reduction of tumor growth. These results demonstrate the great potential of the combined treatment of WIP1 and miR-21 inhibitors for the trastuzumab-resistant HER2+ breast cancers.

关键词： Breast cancer Cancer genomics Cancer therapy

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An intermediate level of abstraction for computational systems chemistry

arXiv

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arXiv 2017年

作者： Andersen, Jakob L. Flamm, Christoph Merkle, Daniel Stadler, Peter F. Earth-Life Science Institute Tokyo Institute of Technology Tokyo152-8550 Japan Department of Mathematics and Computer Science University of Southern Denmark Denmark Research Network Chemistry Meets Microbiology University of Vienna WienA-1090 Austria Institute for Theoretical Chemistry University of Vienna Austria Department of Computer Science University of Leipzig Germany Max Planck Institute for Mathematics in the Sciences Leipzig Germany Fraunhofer Institute for Cell Therapy and Immunology Leipzig Germany Center for non-coding RNA in Technology Health University of Copenhagen Denmark Santa Fe Institute Santa Fe United States

Computational techniques are required for narrowing down the vast space of possibilities to plausible prebiotic scenarios, since precise information on the molecular composition, the dominant reaction chemistry, and the conditions for that era are scarce. The exploration of large chemical reaction networks is a central aspect in this endeavour. While quantum chemical methods can accurately predict the structures and reactivities of small molecules, they are not efficient enough to cope with large-scale reaction systems. The formalization of chemical reactions as graph grammars provides a generative system, well grounded in category theory, at the right level of abstraction for the analysis of large and complex reaction networks. An extension of the basic formalism into the realm of integer hyperflows allows for the identification of complex reaction patterns, such as auto-catalysis, in large reaction networks using optimization techniques. Copyright © 2017, The Authors. All rights reserved.

关键词： Formal languages

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P-219 The role of the putative tumor suppressor protein spinophilin in colorectal cancer

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Annals of Oncology 2015年 26卷 iv64-iv64页

作者： V. Stiegelbauer A. Ress D. Schwarzenbacher A. Deutsch S. Perakis H. Ling C. Ivan G. Calin A. Gerger B. Rinner M. Pichler Division of Oncology Department of Internal Medicine Medical University of Graz Graz Austria Division of Haematology Department of Internal Medicine Medical University of Graz Graz Austria Department of Experimental Therapeutics University of Texas MD Anderson Cancer Center Houston Texas Center for RNA Interference and Non-Coding RNAs The University of Texas MD Anderson Cancer Center Houston Texas Center for Medical Research Medical University of Graz Graz Austria

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Author Correction: Regulation of hnRNPA1 by micrornas controls the miR-18a-K-RAS axis in chemotherapy-resistant ovarian cancer

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Cell discovery 2023年第1期9卷 111页

作者： Cristian Rodriguez-Aguayo Paloma Del C Monroig Roxana S Redis Emine Bayraktar Maria I Almeida Cristina Ivan Enrique Fuentes-Mattei Mohammed H Rashed Arturo Chavez-Reyes Bulent Ozpolat Rahul Mitra Anil K Sood George A Calin Gabriel Lopez-Berestein Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston TX USA. Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston TX USA. Instituto de Investigação e Inovação em Saúde/Institute for Research and Innovation in Health (I3S) and Instituto de Engenharia Biomédica (INEB) University of Porto Porto Portugal. Department of Pharmacology and Toxicology Faculty of Pharmacy The University of Al-Azhar Cairo Egypt. Center for Research and Advanced Studies National Polytechnic Institute (CINVESTAV del IPN) Monterrey Mexico. Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston TX USA. glopez@***. Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston TX USA. glopez@***. Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center Houston TX USA. glopez@***.

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Discovery of a molecular glue that enhances UPRmt to restore proteostasis via TRKA-GRB2-EVI1-CRLS1 axis

Discovery of a molecular glue that enhances UPRmt to restore...

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2022生物物理大会

作者： Li-Feng-Rong Qi Shuai Liu Qiuyuan Fang Cheng Qian Chao Peng Yuci Liu Peng Yang Ping Wu Ling Shan Qinghua Cui Liangyi Chen Wei Yang Ping Li Xiaojun Xu State Key Laboratory of Natural Medicines China Pharmaceutical University Department of Biophysics and Department of Neurosurgery of the First Affiliated Hospital Zhejiang University School of Medicine National Facility for Protein Science in Shanghai Zhangjiang Lab Shanghai Advanced Research Institute Chinese Academy of Science Shanghai Science Research Center Chinese Academy of Sciences Dept.Neuropsychiatric Disorders Netherlands Institute for Neuroscience An Institute of the Royal Netherlands Academy of Arts and Sciences Department of Biomedical Informatics School of Basic Medical Sciences Key Laboratory of Molecular Cardiovascular Sciences of the Ministry of Education Center for Non-Coding RNA Medicine Peking University Health Science Center Beijing PKU-IDG/McGovern Institute for Brain Research

Lowering proteotoxicity is a potentially powerful approach for the treatment of neurological disorders, such as Parkinson's disease. The unfolded protein response(UPR) is a major mechanism that preserves the network maintaining cellular proteostasis. In the present study, we developed the screening strategy to discover compounds that significantly enhanced the activation of mitochondrial UPR(UPRmt)through increasing cardiolipin content. We identified that ginsenoside Rg3(Rg3)increased cardiolipin depending on cardiolipin synthase 1(CRLS1) in both worms and in human neural cells. Using LiP-SMap(limited proteolysis-mass spectrometry)strategy, we identified GRB2(growth factor receptor bound protein 2) as a direct target of Rg3 in human neural cells. Rg3 enhances the binding between GRB2 and TRKA(tropomyosin-related kinase A), that transduces signals via phosphrorylation of ERK(extracellular signal-regulated kinase). We provided bioinformatic and experimental evidences showing that EVI1(ecotropic virus integration site-1), the critical oncogenic transcriptional regulator in leukemia, binds to CRLS1 promoter region and stimulated CRLS1 expression and subsequently increased cardiolipin content in the presence of Rg3. Rg3 stimulates alpha-synuclein clearance by promoting mitochondrial peripheral fission and mitophagy. In two Parkinson's disease mouse models, Rg3 restores motor function by protecting nigral dopaminergic neurons dependent on GRB2. Consistently, Rg3 protected iPSC-derived dopaminergic neurons by restoring ERK/CRLS1 signaling and mitochondrial function. Our data recapitulate the TRKA-GRB2-EVI1-CRLS1 axis in maintaining proteostasis in Parkinson's disease via restoring mitochondrial homeostasis.

关键词： Parkinson's disease cardiolipin UPRmt Ginsenoside Rg3 GRB2 TRKA EVI1

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Corrigendum to 'Exosomal mirna confers chemo resistance via targeting Cav1/p-gp/M2-type macrophage axis in ovarian cancer' [EBioMedicine 38 (2018) 100-112]

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EBioMedicine 2020年 52卷 102630页

作者： Pinar Kanlikilicer Recep Bayraktar Merve Denizli Mohammed H Rashed Cristina Ivan Burcu Aslan Rahul Mitra Kubra Karagoz Emine Bayraktar Xinna Zhang Cristian Rodriguez-Aguayo Amr Ahmed El-Arabey Nermin Kahraman Seyda Baydogan Ozgur Ozkayar Michael L Gatza Bulent Ozpolat George A Calin Anil K Sood Gabriel Lopez-Berestein Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center 1901 East Road Unit 1950 Houston TX 77030 USA Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center 1901 East Road Unit 1950 Houston TX 77030 USA. Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston TX USA Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston TX USA. Rutgers Cancer Institute of New Jersey New Brunswick NJ USA. Pharmacology and Toxicology Department Faculty of Pharmacy Al-Azhar University Nasr City Cairo Egypt. Hacettepe University Ankara Turkey. Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston TX USA Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Electronic address: glopez@***.

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