Table 1.
The emerging roles of exosomal circRNAs in the TME.
| Exosomal circRNA | Source cell | Cancer types | Expression | Molecular axis | Functions | Ref. |
|---|---|---|---|---|---|---|
| Exosomal circRNAs and tumor immunity | ||||||
| circRNA-002178 | Lung adenocarcinoma cells | Lung adenocarcinoma | Up | circRNA-002178/miR-34/PDL1/PD1 | Immune escape, T-cell exhaustion | 47 |
| circ-0001068 | Ovarian cancer | Ovarian cancer | Up | circ-0001068/miR-28-5p /PD1 | Immune escape, induce PD1 expression | 48 |
| circ-CPA4 | Non-small cell lung cancer cells | Non-small cell lung cancer | Up | circ-CPA4/let-7 miRNA/PD-L1 | Immune escape | 49 |
| circUHRF1 | Hepatocellular carcinoma cells | Hepatocellular carcinoma | Up | circUHRF1/miR-449c-5p/TIM-3/anti-PD1 | NK cell exhaustion | 27 |
| circ-PDE8A (hsa_circ_0036627) | Pancreatic ductal adenocarcinoma | Pancreatic ductal adenocarcinoma | Up | circ-PDE8A/miR-338/MACC1/MET | Lymphatic invasion and tumor progression, tumor infiltrating lymphocytes | 60 |
| circPACRGL | Colorectal cancer | Colorectal cancer | Up | circPACRGL/miR-142-3p/miR-506-3p-TGF-β1 | Promote proliferation, migration and invasion, differentiation of N1 to N2 neutrophils. | 61 |
| hsa-circ-0048117 | Hypoxia pre-challenged esophageal squamous cell carcinoma cells | Esophageal squamous cell carcinoma | Up | hsa-circ-0048117/miR-140 | Promote M2 macrophage polarization | 52 |
| circFARSA | Non-small cell lung cancer | Non-small cell lung cancer | Up | circFARSA/PTEN/PI3K/AKT/eIF4A3 | Promote M2 macrophage polarization | 53 |
| Exosomal circRNAs and tumor angiogenesis | ||||||
| circ-CCAC1 | Cholangiocarcinoma | Cholangiocarcinoma | Up | circ-CCAC1/miR-514a-5p/ YY1 | Tumor angiogenesis by interacting with epigenetic regulators | 28 |
| circSHKBP1(hsa_circ_0000936) | Gastric cancer | Gastric cancer | Up | circSHKBP1/miR-582-3p/HUR/VEGF | Angiogenesis by acting as RBPs and miRNA "sponges" | 67 |
| circ-RanGAP1 | Gastric cancer | Gastric cancer | Up | circ-RanGAP1/miR-877-3p/VEGFA | Regulate the expression of VEGFA by acting as specific miRNA “sponges” | 68 |
| circFNDC3B | Colorectal cancer | Colorectal cancer | Down | circFNDC3B/miR-97-5p/TIMP3 | Inhibit angiogenesis and progression. | 69 |
| circ-IARS | Pancreatic cancer | Pancreatic cancer | Up | circRNA IARS /miR-122/RhoA /F-actin |
Elevate endothelial cell permeability, facilitate tumor metastasis and invasion. | 71 |
| circRNA-100,338 | Hepatocellular carcinoma cells | Hepatocellular carcinoma | Up | circRNA-100,338/ NOVA2 | Influence the permeability, angiogenesis and proliferation | 72 |
| Exosomal circRNAs and therapeutic resistance | ||||||
| ciRS-122 | Oxaliplatin-resistant colorectal cancer cells | Colorectal cancer | Up | ciRS-122/miR-122/PKM2 | Promote glycolysis to induce chemoresistance | 77 |
| circ_0000338 | FOLFOX-resistant colorectal cancer cells | Colorectal cancer | Up | —— | Induce chemoresistance | 78 |
| circNFIX | Temozolomide-Resistant glioma cells | Glioma | Up | circNFIX/miR-132. | Enhance temozolomide resistance, diagnostic biomarker (AUC 0.885) and prognostic biomarker | 29 |
| circRNA-SORE | Sorafenib-resistant hepatocellular carcinoma cells | Hepatocellular carcinoma | Up | circRNA-SORE/YBX1/PRP19 | Spread sorafenib resistance | 79 |
| Cdr1as | Cisplatin-resistant ovarian cancer | Ovarian cancer | Down | Cdr1as/miR-1270/SCAI | Suppress cisplatin resistance | 80. |
| hsa_circ_0014235 | Non-small cell lung cancer | Non-small cell lung cancer | Up | circ_0014235/miR-520a-5p/CDK4 | Promote cisplatin resistance | 81 |
| mc-COX2 | Chronic lymphocytic leukemia | Chronic lymphocytic leukemia | Up | —— | Strengthen drug resistance | 82 |
| Exosomal circRNAs and migration and epithelial mesenchymal transition (EMT) | ||||||
| circPRMT5 | Urothelial carcinoma of the bladder | Urothelial carcinoma of the bladder | Up | circPRMT5/miR-30c/SNAIL1/E-cadherin | Epithelial mesenchymal transition (EMT), biomarker of metastasis | 85 |
| circ_MMP2 (hsa_circ_0039411) | Hepatocellular carcinoma cells | Hepatocellular carcinoma | Up | circ_MMP2/miR-136-5p/MMP2 | Enhance the EMT process and invasion | 86 |
| circIFT80 | colorectal cancer | Colorectal cancer | Up | circIFT80/miR-1236-3p/HOXB7 | Promote growth, proliferation, migration, and invasion via EMT | 87 |
| circRNA_100284 | Arsenite-transformed human hepatic epithelial cells | Carcinogenesis induced by Arsenic | Up | circRNA_100284/microRNA-217 | Accelerate the cell cycle and promote cell proliferation | 88 |
| circ-0000284 | Cholangiocarcinoma cells | Cholangiocarcinoma | Up | circ-0000284/miR-637/LY6E | Promote proliferation and migration, suppress apoptosis | 89 |
| circRASSF2 | Laryngeal squamous cell carcinoma | Laryngeal squamous cell carcinoma | Up | circRASSF2 /miR-302b-3p/IGF-1R | Enhance proliferation, migration, and invasion | 90 |
| Exosomal circRNAs and tumor metastasis | ||||||
| circ-PDE8A (hsa_circ_0036627) | Pancreatic ductal adenocarcinoma | Pancreatic ductal adenocarcinoma | Up | circ-PDE8A/miR-338/MACC1/MET | Lymphatic invasion and tumor progression, tumor infiltrating lymphocytes | 60. |
| circPUM1 | Ovarian cancer | Ovarian cancer | Up | circPUM1/miR-615-5p/ miR-6753-5p/NF-κB/ MMP2 | Act on peritoneal mesothelial cells and promote metastasis | 92 |
| circNRIP1 | Gastric cancer | Gastric cancer | Up | circNRIP1/miR-149-5p/AKT1/mTOR | Promote EMT and metastasis | 93 |
| circPTGR1 | Hepatocellular carcinoma | Hepatocellular carcinoma | Up | circPTGR1/miR449a/MET | Promote metastasis and invasion | 95 |
| circWHSC1 | Ovarian cancer | Ovarian cancer | Up | circWHSC1/miR-145 /miR-1182/MUC1 /hTERT | Induce tumor metastasis through acting on peritoneal mesothelium | 96 |
| Exosomal circRNAs and tumor metabolism | ||||||
| circ-DB | Adipocytes | Hepatocellular carcinoma | Up | circ-DB/miR-34a/USP7/Cyclin A2 | Promote tumorigenesis and metastasis | 109 |
| ciRS-133 (circ-0010522) | Gastric cancer cells | Gastric cancer | Up | ciRS-133/miR-133/ PRDM16 | Promote white adipose browning, aggravate tumor cachexia and increase oxygen consumption | 110 |
| circ-MEMO1 | Non-small cell lung cancer | Non-small cell lung cancer | Up | circ-MEMO1/miR-101-3p/KRAS | Facilitate progression and glycolysis | 112 |
| circ-133 | Hypoxic colorectal cancer cells | Colorectal cancer | Up | circ-133 /miR-133a/GEF-H1/RhoA | Promote tumor metastasis and migration | 119 |
| circHIF1A | Hypoxic cancer-associated fibroblasts | Breast cancer | Up | circHIF1A/miR-580-5p/CD44 | Promote breast cancer cell proliferation and stemness | 121 |
| circSLC7A6 | Cancer-associated fibroblasts | Colorectal cancer | Up | circSLC7A6/ CXCR5 | Promote colorectal cancer cell proliferation and invasion | 122 |