Table 2.
The emerging role and mechanistic axis of circRNAs associated with the TME
| Interaction with TME | CircRNA name | Expression | Function | Cancer types | Biological activities | Clinical correlation | Molecular axis |
|---|---|---|---|---|---|---|---|
| circRNAs and CAEs | circ-MYLK | Upregulated | oncogene | Breast cancer | Proliferation, migration, apoptosis, angiogenesis, metastasis, EMT | TNM stage, pathological grade | circ-MYLK/miR-29a/VEGFA/VEGFR2 |
| circ-SMARCA5 | Downregulated | tumor suppressor | Glioblastoma multiform | Angiogenesis | Overall Survival, Progression-Free Survival | circ-SMARCA5/SRSF1/VEGFA | |
| circ-DICER1 | Upregulated | oncogene | Glioma | Proliferation, migration, angiogenesis | / | MOV10/circ-DICER1/ miR-103a-3p/miR-382-5p/ZIC4 | |
| circ-SHKBP1 | Upregulated | oncogene | Glioma | Proliferation, migration, angiogenesis | / | circ-SHKBP1/miR-544a/FOXP1, circ-SHKBP1/miR-379/FOXP2 | |
| circ-IARS | Upregulated | oncogene | Pancreatic ductal adenocarcinoma | Invasion, metastasis, endothelial monolayer permeability | Vascular invasion, TNM stage, liver metastasis, postoperative survival time | circ-IARS/miR-122/RhoA/F-actin/ZO-1 | |
| circ-HIPK3 | Downregulated | tumor suppressor | Bladder cancer | Proliferation, migration, invasion, angiogenesis, metastasis | Pathological grade, tumor invasion, lymph node metastasis | circ-HIPK3/miR-558/HPSE | |
| ciRS-7 | Upregulated | oncogene | Multiple tumours | Angiogenesis, immune and stromal infiltration, ECM organization, integrin and collagen binding | / | cir-DR1as/TGF-β signaling pathway/ECM–receptor interaction | |
| circRNAs and immune cells | ciRS-7 | Upregulated | oncogened | Esophageal squamous cell carcinoma | Proliferation, migration, invasion, metastasis | TNM stage, pathological grade, overall survival, disease-free survival | ciRS-7miR-7/KLF4/NF-κB |
| Multiple tumours | Angiogenesis, immune and stromal infiltration, ECM organization, integrin and collagen binding | / | cir-DR1as/TGF-β signaling pathway/ECM– receptor interaction | ||||
| has_circ_0020397 | Upregulated | oncogene | Colorectal cancer | Proliferation, invasion, apoptosis | / | has_circ_0020397/miR-138/TERT/PD-L1 | |
| hsa_circ_0064428 | Downregulated | tumor suppressor | Hepatocellular carcinoma | / | Tumour size, metastasis, overall survival | / | |
| circRNA-000911 | Downregulated | tumor suppressor | Breast cancer | Proliferation, migration and invasion, apoptosis | / | circ-000911/ miR-449a /Notch1/NF-κB | |
| circ-0000977 | Upregulated | oncogene | Pancreatic cancer | Immune escape, induction by hypoxia | / | circ-0000977/miR-153/HIF1α/ADAM1 | |
| circ-Foxo3 | Downregulated | tumor suppressor | Breast cancer | Proliferation, apoptosis, tumor growth | / | circ-Foxo3/MDM2/P53/Foxo3 | |
| CircRNAs and CAFs | ciRS-7 | Upregulated | oncogene | Multiple tumours | Angiogenesis, immune and stromal infiltration, ECM organization, integrin and collagen binding | / | cir-DR1as/TGF-β signaling pathway/ECM– receptor interaction |
| circRNAs and CSCs | hg19_circ_0005033 | Upregulated | oncogene | Laryngeal squamous cell carcinoma | Proliferation, migration, invasion, chemotherapy resistance | / | hg19_circ_0005033/miR-4521/miR-339-5p/STA T5A |
| circRNAs and hypoxia | circ-DENND2A | Upregulated | oncogene | Glioma | Migration, invasion, induction by hypoxia | / | circ-DENND2A/miR-625-5p/HIF1α |
| circ-PIP5K1A | Upregulated | oncogene | Non-small cell lung cancer | Proliferation, invasion, migration, metastasis, EMT | / | circ-PIP5K1A/miR-600/HIF-1α | |
| circ-0000977 | Upregulated | oncogene | Pancreatic cancer | Immune escape, induction by hypoxia | / | circ-0000977/miR-153/HIF1α/ADAM1 | |
| circ-CDR1as | Downregulated | tumor suppressor | Ovarian cancer | Proliferation, migration, invasion | / | circ-CDR1as/miR-135b-5p/HIF1AN | |
| circ-DENND4C | Upregulated | oncogene | Breast cancer | Proliferation, induction by hypoxia | / | HIF1α/circ-DENN4C | |
| circRNAs and ECM | hsa_circ_0000096 | Downregulated | tumor suppressor | Gastric cacner | Proliferation, migration | Gender, invasion, TNM stage | hsa_circ_0000096/MMP2/MMP9 |
| hsa_circ_0000064 | Upregulated | oncogene | Non-small cell lung cancer | Proliferation, cell cycle, apoptosis, migration, invasion | T stage, TNM stage, lymph node metastasis | hsa_circ_0000064/MMP2/MMP9 | |
| ciRS-7 | Upregulated | oncogene | Multiple tumours | Angiogenesis, immune and stromal infiltration, ECM organization, integrin and collagen binding | / | cir-DR1as/TGF-β signaling pathway/ECM– receptor interaction | |
| circ-ERBB2 | Upregulated | oncogene | Gastric cacner | Proliferation, apoptosis, migration, invasion | Tumor size, invasion depth, overall survival | circ-ERBB2/miR-637/MMP-19 | |
| hsa_circ_0044520 | Upregulated | / | Laryngeal Squamous Cell Carcinoma | Collagen synthesis | / | hsa_circ_0044520/COL1A1 | |
| hsa_circ_0044529 | Upregulated | / | Laryngeal Squamous Cell Carcinoma | Collagen synthesis | / | hsa_circ_0044529/COL1A1 |