ArticleCell death & disease2026
Hypoxia-induced circSPECC1 drives temozolomide resistance in glioblastoma via IGF2BP2-mediated PGK1 mRNA stabilization.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Glioblastoma (GBM) is a notoriously lethal brain tumor, primarily owing to its inevitable resistance to temozolomide (TMZ), a frontline chemotherapy. Hypoxia-driven metabolic adaptations have been implicated in therapeutic failure; however, the role of circular RNAs remains largely underexplored. By integrating multiomics profiling with functional assays in patient-derived GBM cells, orthotopic xenografts, and clinical specimens, this study aimed to elucidate the role of hypoxia-induced hsa_circ_0000745 (circSPECC1) in mediating TMZ resistance. Mechanistic investigation included RNA pulldown, RIP, glycolysis flux analysis, and DNA damage assessment. The circSPECC1 is overexpressed in GBM and correlates with poor prognosis. Hypoxia triggers HIF-1α-mediated transcriptional upregulation of circSPECC1, which scaffolds insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to stabilize phosphoglycerate kinase 1 (PGK1) mRNA. Importantly, circSPECC1/PGK1 axis activation enhances glycolytic flux, blunts TMZ-induced DNA damage, and confers chemoresistance. Targeting circSPECC1 disrupts PGK1-driven glycolysis, restores TMZ sensitivity, and synergizes with TMZ to extend survival in orthotopic GBM models. In conclusion, this study identifies a previously uncharacterized HIF-1α/circSPECC1/IGF2BP2/PGK1 axis that drives metabolic adaptation and TMZ resistance in GBM. Targeting this axis overcomes acquired chemoresistance, positioning circSPECC1 as both a prognostic biomarker and a therapeutic vulnerability in hypoxic GBM niches.
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.