Table 2.
Down-regulated circRNAs in ovarian cancer
| circRNA | Clinical samples/animal model | Assessed cell lines | Targets/regulators/signaling pathways | Description | References |
|---|---|---|---|---|---|
| circPLEKHM3 | 5 tumor tissues and 5 normal ovarian tissues from patients with benign gynaecological diseases/4-week-old female athymic BALB/c nude mice | A2780, OV90 and MDAH2274 | miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis |
↑↑ circPLEKHM3: ↓ cell growth, migration and EMT process Patients with low levels of circPLEKHM3 showed a worse prognosis |
[79] |
| circPLEKHM3 | 35 pairs of tumor tissues and ANCTs/5-week-old female BALB/c athymic mice | SKOV3, A2780 and 293T cells | miR-320a/SMG1 axis | Curcumin treatment: ↑ circPLEKHM3 levels: ↓ cell proliferation and ↑ apoptosis | [80] |
| circ_100395 | 60 pairs of tumor tissues and ANCTs | A2780, OV2008, SKOV3, IGROV1 and ES-2 | miR-1228 | ↑↑ circ_100395: ↓ tumor growth, metastasis and EMT process | [90] |
| circ_0078607 | 20 pairs of tumor tissues and ANCTs | SKOV3 and A2780 | miR-518a-5p/Fas axis | ↑↑ circ_0078607: ↓ proliferation and ↑ apoptosis via sponging miR-518a-5p | [81] |
| circ_0078607 | 43 pairs of tumor tissues and ANCTs/female BALB/c nude mice | HEY, ES-2 and IOSE80 | miR-32-5p/SIK1 axis | ↑↑ circ_0078607: ↓ proliferation, migration, invasion, and ↑ apoptosis via sponging miR-32-5p | [82] |
| circ_0078607 | 49 pairs of tumor tissues and ANCTs | – | – | Patients with low levels of circ_0078607 had advanced FIGO stage, higher serum CA125 level, shorter PFS and OS | [83] |
| circATRNL1 | 56 pairs of tumor tissues and ANCTs/6-week-old nude mice | A2780, SKOV3, CAOV‐3, SNU119 and IOSE80 | miR-378/Smad4 axis | ↑↑ circATRNL1: ↓ proliferation, invasion, migration, angiogenesis and ↑ apoptosis | [91] |
| circHIPK3 | 21 high grade EOC and 21 normal ovarian tissues | A2780, SKOV3 and IOSE80 | – | ∆ circHIPK3: ↑ proliferation, migration, and invasion and ↓ apoptosis | [92] |
| circRHOBTB3 | – | ovarian cancer cells | PI3K/AKT signaling pathway | ↑↑ circRHOBTB3: ↓ cell proliferation, metastasis and glycolysis via inactivating PI3K/AKT signaling pathway | [93] |
| circEXOC6B | 60 ovarian cancer patients and 60 healthy controls/BALB/c mic | A2780, SKOV3 and IOSE-80 | miR-376c-3p/FOXO3 axis |
↑↑ circEXOC6B: ↓ proliferation, motility and chemoresistance of ovarian cancer cells to PTX via sponging miR-376c-3p Low levels of circEXOC6B were correlated with malignant pathological characteristics in ovarian cancer patients |
[84] |
| circEXOC6B | – | A2870, SKOV3, OVCAR3 and IOSE80 | miR-421/RUS1 axis | ↑↑ circEXOC6B: ↓ proliferation, invasion and ↑ apoptosis via sponging miR-421 | [85] |
| circ9119 | 40 ovarian cancer patients and 10 normal controls/5-week old female BALB/c nude mice | SKOV-3, HO-8910, A2780, ES-2, CAOV3, and OVCAR3 and FTE187 | miR-21 and PTEN/Akt pathway | ↑↑ circ9119: ↓ proliferation, viability and ↑ apoptosis | [86] |
| CDR1as | 65 ovarian cancer patients and 37 normal controls | HO8910 and A2780 | miR-135b-5p/HIF1AN axis | ↑↑ CDR1as: ↓ proliferation, invasion and migration | [87] |
| Cdr1as | 66 pairs of tumor tissues and ANCTs/4-week-old BALB/c female athymic mice | A2780, SKOV-3 and IOSE-80 | miR-1270/SCAI axis | ↑↑ CDR1as: ↓ proliferation and ↑ cisplatin-induced cell apoptosis in ovarian cancer cells via sponging miR-1270 | [88] |
| circRNA1656 | 60 HGSOC tissues and 60 benign ovarian tissues | SKOV-3, HO 8910, A2780 and OVCAR-3 | – | Downregulation of circRNA1656 was correlated with the FIGO stage of HGSOC | [94] |
| circ-ITCH | 45 pairs of tumor tissues and ANCTs/5-week-old BALB/c nude mice | A2780, OVCAR3 and ISOE80 | miR-106a/CDH1 axis |
↑↑ circ-ITCH: ↓ proliferation, invasion, glycolysis and ↑ apoptosis via sponging miR-106a Levels of circ-ITCH were positively associated with 5-year OS of patients |
[78] |
| circ-ITCH | 75 pairs of tumor tissues and ANCTs | UWB1.289 and UWB1.289 + BRCA1 | lncRNA HULC | ↑↑ circ-ITCH: ↓ proliferation via downregulating HULC | [77] |
| circ-ITCH | – | SKOV3, A-2780, OVCAR-3, HO-8910 and IOSE80 | miR-10a | ↑↑ circ-ITCH: ↓ proliferation and ↑ apoptosis via sponging miR-10a | [95] |
| circ-ITCH | 20 pairs of tumor tissues and ANCTs/6-weeks-old female BALB/c nude mice | SK-OV-3 and Caov-3 | miR-145/RASA1 axis | ↑↑ circ-ITCH: ↓ viability and motility by CCK8, cell cycle, wound healing assay and invasion via sponging miR-145 | [96] |
| circ-ITCH | 77 pairs of tumor tissues and ANCTs | SKOV3 and OVCAR-3 | – |
High levels of circ-ITCH were associated with small tumor size, decreased FIGO stage and prolonged OS ↑↑ circ-ITCH: ↓ proliferation and ↑ apoptosis |
[97] |
| circBNC2 | 83 EOC patients, 83 benign ovarian cysts, and 83 healthy controls | – | – | CircBNC2 was found to be downregulated in EOC and could be promising novel biomarker for EOC | [89] |
| circMTO1 | 48 pairs of tumor tissues and ANCTs | SKOV3 and OVCAR3 and IOSE80 | miR-182-5p/KLF15 axis | ↑↑ circMTO1: ↓ proliferation and invasion | [98] |
| circ_0007444 | 87 pairs of tumor tissues and ANCTs/5-week-old female nude mice | SKOV3, OV420, A2780, CAOV3, OVCAR3 and HOSEpiC | miR-570-3p/PTEN axis |
↑↑ circ_0007444: ↓ proliferation, migration, and invasion, and ↑ apoptosis via sponging miR-570-3p Low levels of circ_0007444 were correlated with advanced tumor stage and grade, large tumor size, and low 60-month percent survival |
[99] |
| circLARP4 | 78 pairs of tumor tissues and ANCTs | – | – | Low levels of circLARP4 were correlated with FIGO stage, lymph node metastases and poor prognosis of OC patients | [100] |
| circLARP4 | – | SKOV3, A2780, SW626, OVCAR3, OVCAR4 and HOSEpiC | miR-513b-5p/LARP4 axis | ↑↑ circLARP4: ↑proliferation, invasion and migration | [101] |
| hsa_circ_0007874 | 4-week-old BALB/c nude mice | IGROV1, A2780, ES‐2, OV2008, and SKOV3 and ISOE80 | miR-760/SOCS3 axis | ↑↑ hsa_circ_0007874: ↓ proliferation and migration | [102] |
| circN4BP2L2 | 126 EOC patients, 126 benign ovarian cyst, and 126 healthy controls | SKOV3, OVCAR3, CAOV3, HO8910, TOV-112D, and IOSE80 | – |
↑↑ circN4BP2L2: ↓ migration and invasion Low levels of circN4BP2L2 were correlated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC |
[103] |
∆ knock-down or deletion, ANCTs adjacent non-cancerous tissues, EOC epithelial ovarian cancer, OS overall survival, EMT epithelial-mesenchymal transition, PFS progression-free survival, DFS disease-free survival, PTX paclitaxel, DDP cisplatin, HGSOC high-grade serous ovarian cancer, GTEx genotype-tissue expression, FIGO International Federation of Gynecology and Obstetrics, SOC high-grade serous ovarian cancer