ArticleLaboratory investigation; a journal of technical methods and pathology2016
Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Altered Expression of Ribosome Biogenesis Regulators (TP53, C-MYC, FBL, and NCL) in Precursor B-cell Acute Lymphoblastic Leukemia and Neuroblastoma.Current issues in molecular biology · 2026Article
- Targeted immune activation in pediatric solid tumors: opportunities to complement local control approaches.Frontiers in immunology · 2023Review
- The role of toll-like receptors (TLRs) in pan-cancer.Annals of medicine · 2022Article
- Epigenetic state determines inflammatory sensing in neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model.Scientific reports · 2021Article
- TLR5: A prognostic and monitoring indicator for triple-negative breast cancer.Cell death & disease · 2019Article
- Developing preclinical models of neuroblastoma: driving therapeutic testing.BMC biomedical engineering · 2019Review
- Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma.Cancer science · 2018Article
- The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in ApcJournal of biomedical science · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma (NB) is the deadliest pediatric solid tumor due to its pleomorphic molecular characteristics. In the innate immune system, toll-like receptor 3 (TLR3) recognizes viral double-stranded RNAs to initiate immune signaling. Positive TLR3 expression indicates a favorable prognosis in NB patients, and is associated with MYCN-non-amplified. However, TLR3-mediated innate immune responses remain elusive in NB. In this study, we attempted to dissect the molecular mechanism underlying TLR3-agonist polyinosinic-polycytidylic acid [poly(I:C)] treatment in NB in vivo. We established NB xenograft models in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with MYCN-amplified SK-N-DZ (DZ) cells or MYCN-non-amplified SK-N-AS (AS) cells. Poly(I:C) treatment led to significant tumor regression in AS xenografts, but not in DZ xenografts. Through immunohistochemical analysis, significant suppression of tumor proliferation, downregulation of c-Myc expression, and upregulation of TLR3 expression were found in the treatment group. Poly(I:C) inducing activation of TLR3/IRF3-mediated innate immunity associated with downregulation of c-Myc can be found in MYCN-non-amplified SK-N-AS cells, but not in MYCN-amplified BE(2)-M17 cells. Knockdown of TLR3 disturbed poly(I:C)-induced suppression of c-Myc and upregulation of p-IRF3 in AS cells. Furthermore, poly(I:C) treatment upregulated active NF-κB, mitochondrial antioxidant manganese superoxide dismutase and 8-hydroxydeoxyguanosine, which works with reactive oxygen species (ROS) generation and DNA damage. Upregulation of active caspase 3 and cleaved poly [ADP-ribose] polymerase 1 were found in poly(I:C)-treated AS xenografts, which indicates the induction of apoptosis. Thus, our results suggest that c-Myc overexpression may increase sensitivity to poly(I:C)-induced tumor growth arrest and ROS-mediated apoptosis in NB. This study demonstrates that c-Myc protein expression has an important role in TLR3-induced innate immune responses, providing future treatment recommendations.
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