https://scholars.lib.ntu.edu.tw/handle/123456789/469984
標題: | MDA5 complements TLR3 in suppression of neuroblastoma | 作者: | WEN-MING HSU Huang C.-C. Lee H.-Y. Wu P.-Y. Wu M.-T. Chuang H.-C. Lin L.-L. Chuang J.-H. |
公開日期: | 2015 | 出版社: | Impact Journals LLC | 卷: | 6 | 期: | 28 | 起(迄)頁: | 24935-24946 | 來源出版物: | Oncotarget | 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 differentiationassociated 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-NAS (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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84944472825&doi=10.18632%2foncotarget.4511&partnerID=40&md5=5072b3c639c2c3405b585117b262fcaf https://scholars.lib.ntu.edu.tw/handle/123456789/469984 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.4511 | SDG/關鍵字: | caspase 3; caspase 9; melanoma differentiation gene 5; messenger RNA; mitochondrial antiviral signaling protein; oncoprotein; polyinosinic polycytidylic acid; reactive oxygen metabolite; retinoic acid inducible protein I; small interfering RNA; toll like receptor 3; unclassified drug; caspase 3; caspase 9; DDX58 protein, human; DEAD box protein; IFIH1 protein, human; interferon induced helicase C domain containing protein 1; polyinosinic polycytidylic acid; reactive oxygen metabolite; retinoic acid inducible protein I; TLR3 protein, human; toll like receptor 3; apoptosis; Article; cancer inhibition; controlled study; drug targeting; enzyme activation; gene expression regulation; gene overexpression; gene silencing; gene targeting; human; human cell; MAVS gene; MDA5 gene; neuroblastoma; neuroblastoma cell line; protein expression; RIG I gene; TLR3 gene; agonists; antagonists and inhibitors; child; drug effects; female; genetics; infant; Kaplan Meier method; male; metabolism; mitochondrion; neuroblastoma; newborn; pathology; preschool child; reverse transcription polymerase chain reaction; RNA interference; Western blotting; Apoptosis; Blotting, Western; Caspase 3; Caspase 9; Child; Child, Preschool; DEAD Box Protein 58; DEAD-box RNA Helicases; Female; Gene Expression Regulation, Neoplastic; Humans; Infant; Infant, Newborn; Interferon-Induced Helicase, IFIH1; Kaplan-Meier Estimate; Male; Mitochondria; Neuroblastoma; Poly I-C; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Toll-Like Receptor 3 |
顯示於: | 醫學系 |
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