ArticleOncotarget2016
Gene silencing of indoleamine 2,3-dioxygenase 2 in melanoma cells induces apoptosis through the suppression of NAD+ and inhibits in vivo tumor growth.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Epacadostat and Olaparib Synergistically Inhibit the Growth of BRCA-Proficient Triple-Negative Breast Cancer by Suppressing the Expression of BRCA1 and RAD51.Molecules (Basel, Switzerland) · 2026Article
- Promising Gastric Cancer Biomarkers-Focus on Tryptophan Metabolism via the Kynurenine Pathway.International journal of molecular sciences · 2025Review
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- Review
- IDO1-mediated kynurenine production inhibits IGFBP5 signaling to promote 5-fluorouracil-induced senescence escape and chemoresistance in colorectal cancer.American journal of cancer research · 2024Article
- Membrane Localization and Phosphorylation of Indoleamine 2,3-Dioxygenase 2 (IDO2) in A549 Human Lung Adenocarcinoma Cells: First Steps in Exploring Its Signaling Function.International journal of molecular sciences · 2023Article
- The role of MSCs and CAR-MSCs in cellular immunotherapy.Cell communication and signaling : CCS · 2023Review
- Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer.Scientific reports · 2023Article
- The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer.Frontiers in oncology · 2023Review
- Article
- Indoleamine 2, 3-Dioxygenase 1 Mediates Survival Signals in Chronic Lymphocytic LeukemiaFrontiers in immunology · 2022Article
- Article
- Current Challenges for IDO2 as Target in Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Persistent Regulation of Tumor Hypoxia Microenvironment via a Bioinspired Pt-Based Oxygen Nanogenerator for Multimodal Imaging-Guided Synergistic Phototherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- miRNA-5119 regulates immune checkpoints in dendritic cells to enhance breast cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2020Article
- Immunomodulation of MSCs and MSC-Derived Extracellular Vesicles in Osteoarthritis.Frontiers in bioengineering and biotechnology · 2020Review
- The therapeutic potential of targeting tryptophan catabolism in cancer.British journal of cancer · 2020Review
- Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity.Frontiers in immunology · 2020Article
- Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development.Current oncology reports · 2019Review
- Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?Frontiers in cellular and infection microbiology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indoleamine 2,3-dioxygenase 2 (IDO2) is a newly discovered enzyme that catalyzes the initial and rate-limiting step in the degradation of tryptophan. As a homologous protein of IDO1, IDO2 plays an inhibitory role in T cell proliferation, and it is essential for regulatory T cell (Treg) generation in healthy conditions. Little is known about the immune-independent functions of IDO2 relevant to its specific contributions to physiology and pathophysiology in cancer cells. The purpose of this study was to assess the impact of IDO2 gene silencing as a way to inhibit B16-BL6 cancer cells in a murine model. Here, for the first time, we show that knockdown of IDO2 using small interfering RNA (siRNA) inhibits cancer cell proliferation, arrests cell cycle in G1, induces greater cell apoptosis, and reduces cell migration in vitro. Knockdown of IDO2 decreased the generation of nicotinamide adenine dinucleotide (NAD+) while increasing the generation of reactive oxygen species (ROS). We further demonstrate that cell apoptosis, induced by IDO2 downregulation, can be weakened by addition of exogenous NAD+, suggesting a novel mechanism by which IDO2 promotes tumor growth through its metabolite product NAD+. In addition to in vitro findings, we also demonstrate that IDO2 silencing in tumor cells using short hairpin RNA (shRNA) delayed tumor formation and arrested tumor growth in vivo. In conclusion, this study demonstrates a new non-immune-associated mechanism of IDO2 in vitro and IDO2 expression in B16-BL6 cells contributes to cancer development and progression. Our research provides evidence of a novel target for gene silencing that has the potential to enhance cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.