Table 1 The HIF-1α dependent or independent regulation of hypoxia-responsive circRNAs in hypoxic tumor microenvironment.
Hypoxia-responsive circRNAs | Status upon hypoxia | HIF involvement | Cancer types | Clinical association | Functional impact | Interactor | Target/effect | Mechanistic Classification | Refs |
|---|---|---|---|---|---|---|---|---|---|
circDENND4C | Up-regulated | HIF-1α dependent | Breast cancer | Associated with tumor node metastasis stage lymph node metastasis and tumor size | Glycolysis↑ Migration↑ Invasion↑ | miR-200b miR-200c | Increase glucose consumption, Lactate production, HK2 protein level, Migration, Invasion. | Sequestration of miRNAs (Down-regulation of miR-200b and miR-200c-mediated repression of glycolysis, migration and invasion) | [27] |
circZNF292 (circRNA-403658) | Up-regulated | HIF-1α dependent | Bladder cancer | Promoting cancer progression | Cell growth↑ Glycolysis↑ Angiogenesis↑ Apoptosis↓ | LDHA | LDHA promotor | Transcriptional regulation promoting the activity of the LDHA promoter | [29] |
circDENND4C | Up-regulated | HIF-1α dependent | Breast cancer | Positively correlated to tumor size | Proliferation↑ | N.D. | N.D. | Unclear mechanism | [46] |
circHIPK3 | Up-regulated | HIF-2α dependent | Gastric Cancer | Shorter overall survival (OS) | Migration↑ Invasion↑ | miR-653-5p miR-338-3p | Activation of downstream ERK and AKT pathways | Sequestration of miRNAs (Down-regulation of miR-653-5p and miR-338-3p-mediated repression of NRP1 expression) | [28] |
circSETDB1 (hsa-circ-0003439) | Up-regulated | HIF-1α pathway related | Lung adenocarcinoma (LUAD) | Correlated with T stage and lymph node metastasis | Migration↑ Invasion↑ Proliferation↑ | miR-7 | Promoted lung cancer EMT | Sequestration of miRNAs (Down-regulation of miR-7-mediated repression of Sp1 expression) | [33] |
circDENND2A | Up-regulated | HIF-1α related | Glioma | Enhances glioma metastases | Migration↑ Invasion↑ | miR-625-5p | HIF1α or SOX2 | Sequestration of miRNAs (Down-regulation of miR-625-5p-mediated repression of HIF1α or SOX2 expression) | [30] |
circ_0008193 | Down-regulated | HIF-1α related | Lung adenocarcinoma (LUAD) | Correlated with tumor size and lymph node metastasis | Cell viability↓ Glucose uptake↓ Lactate production↓ Migration↓ Invasion↓ | miR-1180-3p | Inhibited LUAD cell proliferation, migration, invasion, and Warburg effect under hypoxia in vitro and in vivo | Sequestration of miRNAs (Down-regulation of miR-1180-3p-mediated repression of TRIM62 expression) | [32] |
circ-EPHB4 (hsa-circ-0001730) | Down-regulated | HIF-1α related | Hepatocellular carcinoma | Negatively correlated with tumor weight, size, and metastasis foci | tumorigenesis↓ Tumor development↓ Metastasis↓ | N.D. | HIF1α | Unclear mechanism | [31] |
circELP3 | Up-regulated | HIF-1α independent neither the HIF-associated pathway nor increased circulation | Bladder cancer | Associated tumor grade and lymph node metastasis | Proliferation↑ Self-renewal capacity↑ Cisplatin resistance↑ | OCT4,SOX2 Nanog | Promote cisplatin resistance | Unclear mechanism | [34] |
circZNF292 | Up-regulated | HIF-1α independent | Hepatoma cells | N.D. | Proliferation↑ Vasculogenic mimicry↑ Radioresistance↑ | SOX9 | Enhanced Wnt/β-catenin pathway activity | Sequestration of Protein Binding to SOX9 protein in cytoplasm and inhibited its nuclear translocation | [47] |
circHIF1A | Up-regulated | HIF-1α independent | Cancer-associated fibroblasts (CAFs) in breast cancer | N.D. | Cell proliferation↑ Stemness↑ | miR-580-5p | Promoted breast cancer cell proliferation and stemness | Sequestration of miRNAs (Down-regulation of miR-580-5p-mediated repression of CD44 expression) | [36] |
