ArticleAutophagy2016
A novel tumor-promoting mechanism of IL6 and the therapeutic efficacy of tocilizumab: Hypoxia-induced IL6 is a potent autophagy initiator in glioblastoma via the p-STAT3-MIR155-3p-CREBRF pathway.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 3 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- RNA Expression Signatures in Glioblastoma: A Systematic Review of Tumour Biology and Therapeutic Targets.Oncology research · 2025Pooled it
- Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma.Frontiers in immunology · 2022Pooled it
- Clinicopathological and Prognostic Roles of STAT3 and Its Phosphorylation in Glioma.Disease markers · 2020Pooled it
- Uncovering MYOF as a novel therapeutic target in glioblastoma: mechanistic insights and drug discovery.Cell death discovery · 2026Article
- Senescent cell clearance suppresses post-radiotherapy glioblastoma recurrence via the IL-6/JAK2/STAT3 pathway.Molecular and cellular biochemistry · 2026Article
- Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.International journal of molecular sciences · 2025Article
- LncRNA EUDAL shapes tumor cell response to hypoxia-induced constitutive EGFR activation and promotes chemoresistance in oral cancer.International journal of oral science · 2025Article
- Neoadjuvant PD-1 blockade induces the autophagy of immune cells: a new target for synergistic therapy of recurrent glioblastoma.Biochemistry and biophysics reports · 2025Article
- The regulation of miR-155 strand selection by CELF2, FUBP1 and KSRP proteins.Scientific reports · 2025Article
- The role of non-coding RNAs in the regulation of cell death pathways in melanoma.Discover oncology · 2025Review
- The Metabolic Orchestration of Immune Evasion in Glioblastoma: From Molecular Perspectives to Therapeutic Vulnerabilities.Cancers · 2025Review
- Granular cytoplasmic inclusions in astrocytes and microglial activation in the fetal brain of pigtail macaques in response to maternal viral infection.Acta neuropathologica communications · 2025Article
- Targeting CREBRF in Cancer: Mechanistic Insights and Future Directions.Biologics : targets & therapy · 2025Review
- Regulation of autophagy by non-coding RNAs in human glioblastoma.Medical oncology (Northwood, London, England) · 2024Review
- Pyrimidine compounds BY4003 and BY4008 inhibit glioblastoma cells growth via modulating JAK3/STAT3 signaling pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma.Cancers · 2024Article
- The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions.Journal of experimental & clinical cancer research : CR · 2024Article
- 'Slicing' glioblastoma drivers with the Swiss cheese model.Trends in cancer · 2024Review
- An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.NPJ precision oncology · 2023Review
- Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia induces protective autophagy in glioblastoma cells and new therapeutic avenues that target this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastomas in response to extensive hypoxia. Hypoxia also induces the upregulation of a specific set of proteins and microRNAs (miRNAs) in a variety of cell types. IL6 (interleukin 6), an inflammatory autocrine and paracrine cytokine that is overexpressed in glioblastoma, has been reported to be a biomarker for poor prognosis because of its tumor-promoting effects. Here, we describe a novel tumor-promoting mechanism of IL6, whereby hypoxia-induced IL6 acts as a potent initiator of autophagy in glioblastoma via the phosphorylated (p)-STAT3-MIR155-3p pathway. IL6 and p-STAT3 levels correlated with the abundance of autophagic cells and HIF1A levels in human glioma tissues and with the grade of human glioma, whereas inhibition of exogenous or endogenous IL6 repressed autophagy in glioblastoma cells in vitro. Knockdown of endogenous MIR155-3p inhibited IL6-induced autophagy, and enforced expression of MIR155-3p restored the anti-autophagic activity of IL6 inhibitors. We show that the hypoxia-IL6-p-STAT3-MIR155-3p-CREBRF-CREB3-ATG5 pathway plays a central role in malignant glioma progression, with blockade of the IL6 receptor by tocilizumab demonstrating a certain level of therapeutic efficacy in a xenograft model in vivo, especially in combination with temozolomide. Moreover, tocilizumab inhibits autophagy by promoting tumor apoptosis. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioma cell autophagy and point toward a possible efficacious adjuvant therapy for glioblastoma patients.
Indexed as
Identifiers
What OpenQuestion holds
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.