http://repository.iitr.ac.in/handle/123456789/20080| Title: | IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type i interferons-dependent and-independent anticancer activity |
| Authors: | Kumar, Sushil Ingle H. Mishra S. Mahla R.S. Kumar A. Kawai T. Akira S. Takaoka A. Raut A.A. Kumar H. |
| Published in: | Cell Death and Disease |
| Abstract: | RIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the production of type I interferons (IFN) and proinflammatory cytokines through a sole adaptor IFN-β promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS and VISA) in antiviral innate immunity. These sensors also have a pivotal role in anticancer activity through induction of apoptosis. However, the mechanism for their anticancer activity is poorly understood. Here, we show that anticancer vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus, Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer cells induces anticancer activity. PolyIC transfection and NDV infection upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in IFN-non-responsive cancer cells show reduced anticancer activity by suppressing apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via IRF3 and IRF7 in type I IFN-dependent and -independent manners. © 2015 Macmillan Publishers Limited All rights reserved. |
| Citation: | Cell Death and Disease, 6(5) |
| URI: | https://doi.org/10.1038/cddis.2015.122 http://repository.iitr.ac.in/handle/123456789/20080 |
| Issue Date: | 2015 |
| Publisher: | Nature Publishing Group |
| Keywords: | adaptor protein cytokine immunological adjuvant interferon interferon beta promoter stimulator 1 interferon regulatory factor 3 interferon regulatory factor 7 oncolytic virus polyinosinic polycytidylic acid retinoic acid inducible protein I unclassified drug BCL2 protein, human BIRC3 protein, human cancer vaccine inhibitor of apoptosis protein interferon interferon regulatory factor 3 interferon regulatory factor 7 IRF3 protein, human IRF7 protein, human PRKCE protein, human protein bcl 2 protein kinase C epsilon signal transducing adaptor protein small interfering RNA TNFSF10 protein, human tumor necrosis factor related apoptosis inducing ligand ubiquitin protein ligase VISA protein, human antineoplastic activity apoptosis Article BCL2 gene BIRC3 gene controlled study cytokine production down regulation gene gene induction genetic transfection human human cell interferon production Newcastle disease virus nonhuman priority journal PRKCE gene protein expression TRAL gene upregulation biosynthesis genetics HEK293 cell line immunology neoplasm pathology RNA interference signal transduction tumor cell line tumor invasion Adaptor Proteins, Signal Transducing Apoptosis Cancer Vaccines Cell Line, Tumor Down-Regulation HEK293 Cells Inhibitor of Apoptosis Proteins Interferon Regulatory Factor-3 Interferon Regulatory Factor-7 Interferon Type I Neoplasm Invasiveness Neoplasms Newcastle disease virus Poly I-C Protein Kinase C-epsilon Proto-Oncogene Proteins c-bcl-2 RNA Interference RNA, Small Interfering Signal Transduction TNF-Related Apoptosis-Inducing Ligand Ubiquitin-Protein Ligases Up-Regulation |
| ISSN: | 20414889 |
| Author Scopus IDs: | 57213855617 55800997500 57209827356 39561382400 57202998869 57189013836 35396685700 56622562000 7004408008 7102422606 |
| Author Affiliations: | Kumar, S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India Ingle, H., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India Mishra, S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India Mahla, R.S., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India Kumar, A., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India Kawai, T., Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan Akira, S., Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka, Japan Takaoka, A., Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Raut, A.A., Pathogenomics Laboratory, ICAR-National Institute of High Security Animal Diseases, OIE Reference Lab for Avian Influenza, Bhopal, India Kumar, H., Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Indore-Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066, India, Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka, Japan |
| Funding Details: | We thank Dr Milind M Vaidya, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India for providing MCF10A cell line. We also thank Dr Toru Kubota, Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan for providing the construct of IRF3/5D. This work is partly supported by research grants SR/S2/RJN-55/2009 and BT/PR6009/GBD/27/382/2012 from Department of Science and technology (DST) and Department of Biotechnology (DBT), Government of India (HK); and Intramural Research Grant of IISER, Bhopal, India. This study was also partly supported by the Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University, Japan (HK and AT). Japan Society for the Promotion of Science, JSPS: 26293107, 26670236; Hokkaido University, HU; Department of Science and Technology, Government of Kerala; Department of Biotechnology, Government of West Bengal, DBT-WB; Indian Institute of Science Education and Research Mohali, IISER |
| Corresponding Author: | Kumar, H.; Laboratory of Immunology, Indore-Bypass Road, India; email: hkumar@iiserb.ac.in |
| Appears in Collections: | Journal Publications [BT] |
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