ArticlePLoS genetics2021
ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- RBM15 Contributes to Bladder Carcinoma Progression via m6A-dependent Stabilization of IFI6 mRNA.Applied biochemistry and biotechnology · 2026Article
- Histopathological Assessment of IFI6- and RSAD2-DNA Aptamers in Oral Squamous Cell Carcinoma: A Preliminary Study Based onBiomedicines · 2026Article
- FOXA1 Transcriptional Repression of PLSCR1 Inhibits Tongue Squamous Cell Carcinoma Progression.Cell biochemistry and biophysics · 2025Article
- Acinar-specific loss of activating transcription factor 3 restricts KRASCell death discovery · 2025Article
- CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma.Genes & diseases · 2025Article
- PER2 interaction with HSP70 promotes cuproptosis in oral squamous carcinoma cells by decreasing AKT stability.Cell death & disease · 2025Article
- Inhibition of p16 and NF-κB Oncogenic Activity in Human Papillomavirus-Infected Cervical Cancer Cells: A New Role for Activating Transcription Factor-3.The Yale journal of biology and medicine · 2025Article
- HOXA5 Derives the Malignant Progression and Cisplatin Resistance of Esophageal Squamous Cell Carcinoma by Regulating USP18-Mediated IFI27 Deubiquitination.Thoracic cancer · 2025Article
- ZNF671 Silencing Affects Signaling Pathways in Head and Neck Cancer via Activation of Oncogenic Non-Coding RNAs.Biomedicines · 2024Article
- Article
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- Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation.PLoS pathogens · 2024Article
- ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling.Cancers · 2024Article
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- Article
- Microglia-specific transcriptional repression of interferon-regulated genes after prolonged stress in mice.Neurobiology of stress · 2022Article
- Single-cell transcriptomic profiling for inferring tumor origin and mechanisms of therapeutic resistance.NPJ precision oncology · 2022Article
- Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response.Cancers · 2022Article
- An IFI6-based hydrogel promotes the healing of radiation-induced skin injury through regulation of the HSF1 activity.Journal of nanobiotechnology · 2022Article
- Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts.PloS one · 2022Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating transcription factor 3 (ATF3) is a key transcription factor involved in regulating cellular stress responses, with different expression levels and functions in different tissues. ATF3 has also been shown to play crucial roles in regulating tumor development and progression, however its potential role in oral squamous cell carcinomas has not been fully explored. In this study, we examined biopsies of tongue squamous cell carcinomas (TSCCs) and found that the nuclear expression level of ATF3 correlated negatively with the differentiation status of TSCCs, which was validated by analysis of the ATGC database. By using gain- or loss- of function analyses of ATF3 in four different TSCC cell lines, we demonstrated that ATF3 negatively regulates the growth and migration of human TSCC cells in vitro. RNA-seq analysis identified two new downstream targets of ATF3, interferon alpha inducible proteins 6 (IFI6) and 27 (IFI27), which were upregulated in ATF3-deleted cells and were downregulated in ATF3-overexpressing cells. Chromatin immunoprecipitation assays showed that ATF3 binds the promoter regions of the IFI6 and IFI27 genes. Both IFI6 and IFI27 were highly expressed in TSCC biopsies and knockdown of either IFI6 or IFI27 in TSCC cells blocked the cell growth and migration induced by the deletion of ATF3. Conversely, overexpression of either IFI6 or IFI27 counteracted the inhibition of TSCC cell growth and migration induced by the overexpression of ATF3. Finally, an in vivo study in mice confirmed those in vitro findings. Our study suggests that ATF3 plays an anti-tumor function in TSCCs through the negative regulation of its downstream targets, IFI6 and IFI27.
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