MDA5 complements TLR3 in suppression of neuroblastoma

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Title:	MDA5 complements TLR3 in suppression of neuroblastoma
Authors:	吳沛翊;Hsu, Wen-Ming;Huang, Chao-Cheng;Lee, Hsin-Yu;Wu, Pei-Yi;Wu, Min-Tsui;Chuang, Hui-Ching;Lin, Li-Ling;Chuang, Jiin-Haur
Contributors:	生醫理工學院生命科學系
Keywords:	Apoptosis - drug effects;Apoptosis - genetics;Blotting, Western;Caspase 3 - genetics;Caspase 3 - metabolism;Caspase 9 - genetics;Caspase 9 - metabolism;Child;Child, Preschool;DEAD Box Protein 58;DEAD-box RNA Helicases - genetics;DEAD-box RNA Helicases - metabolism;Female;Gene Expression Regulation, Neoplastic - drug effects;Humans;Infant;Infant, Newborn;Interferon-Induced Helicase, IFIH1;Kaplan-Meier Estimate;Male;Mitochondria - drug effects;Mitochondria - metabolism;Neuroblastoma - genetics;Neuroblastoma - metabolism;Neuroblastoma - pathology;Poly I-C - pharmacology;Reactive Oxygen Species - antagonists & inhibitors;Reactive Oxygen Species - metabolism;Receptors, Immunologic;Research Paper;Reverse Transcriptase Polymerase Chain Reaction;RNA Interference;Toll-Like Receptor 3 - agonists;Toll-Like Receptor 3 - genetics;Toll-Like Receptor 3 - metabolism
Date:	2015-01-01
Issue Date:	2026-04-23 11:13:19 (UTC+8)
Publisher:	Impact Journals LLC;United States: Impact Journals LLC
Abstract:	摘要： Toll-like receptor3 (TLR3) has been confirmed to be differentially expressed in neuroblastoma (NB), and predicts a favorable prognosis with a high expression in tumor tissues. Treatment with TLR3 agonist--polyinosinic-polycytidylic acid [poly(I:C)] could induce significant but limited apoptosis in TLR3-expressing NB cells, suggesting that other viral RNA sensors, including melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) in the cytosolic compartment might also be implicated in poly(I:C)-induced NB cell death. MDA5 and RIG-I were induced by poly(I:C) to express in two of six NB cell lines, SK-N-AS (AS) and SK-N-FI, which were associated with up-regulation of caspase9 and active caspase3. While knockdown of either MDA5 or RIG-I alone is ineffective to decrease caspase9 and active caspase3, simultaneously targeting MDA5 and TLR3 showed the best effect to rescue poly(I:C) induced up-regulation of mitochondrial antiviral signaling protein (MAVS), caspase9, active caspase3, and apoptosis in AS cells. Over-expression of MDA5 in FaDu cells resulted in significantly less colony formation and more poly(I:C)-induced cell death. Further studies in human NB tissue samples revealed that MDA5 expression in NB tissues predicted a favorable prognosis synergistically with TLR3. Our findings indicate that MDA5 may serve as a complementary role in the TLR3 activated suppression of NB. 其他題名： Oncotarget 出版者： United States: Impact Journals LLC 出版日期： 2015-09-22 出處： Oncotarget, 2015-09, Vol.6 (28), p.24935-24946 版權： Copyright: © 2015 Hsu et al. 2015 識別號： ISSN: 1949-2553 識別號： EISSN: 1949-2553 識別號： DOI: 10.18632/oncotarget.4511 識別號： PMID: 26208481
Appears in Collections:	[Department of Life Science] journal & Dissertation

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