ArticleFrontiers in pharmacology2025
Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed.
- Review
- Research progress on glioma drug resistance: mechanism analysis and therapeutic strategies.Frontiers in pharmacology · 2026Review
- miR-652-5p promoter hypermethylation enhances glioblastoma malignancy through the SDC1/TGFβ2/pERBB4 complex via HIF2α-mediated regulation under hypoxia.Cancer cell international · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: This study investigates whether Hypoxia-Inducible Factor 1 alpha (HIF1α) and Hypoxia-Inducible Factor 2 alpha (HIF2α) coordinately regulate insulin-like growth factor 1 receptor (IGF1R) expression, thereby influencing chemosensitivity in glioblastoma multiforme (GBM). Methods: We analyzed the expression and correlation of HIF1α, HIF2α, and IGF1R in glioma using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Immunohistochemistry (IHC) was performed to detect the expression of HIF1α, HIF2α, and IGF1R in GBM tissues and cells, as well as oxygen tension. Cell cycle analysis, apoptosis assays, lactate dehydrogenase (LDH) release measurements, Western blotting, and xenograft tumor models were employed to explore the synergistic regulation of IGF1R by HIF1α and HIF2α, focusing on activation of the PI3K/AKT signaling pathway and its contribution to GBM drug resistance. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays were used to investigate the binding sites of HIF1α and HIF2α involved in regulating IGF1R. Results: Our study demonstrated that HIF1α and HIF2α were highly expressed in GBM tissues and hypoxia-cultured cells, and their expression positively correlated with IGF1R expression. Simultaneous knockout of HIF1α and HIF2α in GBM cells resulted in the highest LDH release and apoptosis rates under hypoxic conditions, accompanied by the most significant decrease in IGF1R, p-PDK1, and p-AKT levels. Knockout of IGF1R in tumor cells under hypoxia led to an increas of LDH release and apoptosis rates, and reduced phosphorylation of PDK1 and AKT. In addition, we demonstrated that HIF1α and HIF2α promoted IGF1R expression by binding to a specific hypoxia response element (HRE) sequence (5'-GAACGTGCCT-3') within the IGF1R promoter using dual-luciferase reporter system. Conclusion: Glioblastoma cells, residing within a hypoxic microenvironment, exhibit high expression of HIF1α and HIF2α. These transcription factors promote the upregulation of IGF1R, which subsequently activates the PI3K/AKT signaling pathway. This activation, in turn, promotes cell proliferation and chemoresistance, ultimately contributing to tumor malignancy.
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.