Background
Circular RNAs
Biogenesis of circRNAs
Biological properties of circRNAs
Functions of circRNAs
CircRNAs serve as ceRNAs or miRNA sponges
CircRNAs bind with proteins
Potential translation templates of proteins
CircRNAs regulate the splicing of pre-RNA
Regulation of parental gene expression by circRNAs
CircRNAs and GC
Name | Dysregulation | Sponge target | Function | Types of GC tissues and GC cell lines | Ref. |
---|---|---|---|---|---|
circPVT1 | up-regulated | miR-125 family | Independent prognostic indicator; promotes cancer cell proliferation | 187 GC tissue samples with various clinicopathologic features; MGC-803 and AGS GC cell lines | [75] |
circRNA_100269 | downregulated | miR-630 | Inhibits cancer cell proliferation | 112 GC tissue samples with various clinicopathologic features; AGS, MKN-28, MKN-45, BGC-823, MGC-803 and SGC-7901 GC cell lines | [76] |
circNRIP1 | up-regulated | miR-149-5p | Promotes cancer cell proliferation, invasion and migration | 80 GC tissue samples with various clinicopathologic features; BGC-823, AGS, SGC-7901, MGC-803, MKN-45 and HGC-27 GC cell lines | [77] |
circ-DONSON | up-regulated | – | Promotes cancer cell proliferation, invasion and migration | 142 GC tissue samples; BGC-823, AGS, MGC-803, MKN74, HGC-27 and SGC-7901 GC cell lines | [78] |
circRNA0047905 | up-regulated | miR4516 miR1227-5p | Tumor promoter; potential therapy target | 31 GC tissue samples; AGS GC cell line | [79] |
circDLST | up-regulated | miR-502-5p | Promotes cancer cell proliferation, invasion and metastasis | 396 GC tissue samples of various stages; MGC-803, BGC-823, SGC-7901, HGC-27, AGS, MKN-45 and MKN-28 GC cell lines | [80] |
circ_0067997 | up-regulated | miR-515-5p | Promotes cancer cell viability, proliferation and invasion | 48 GC tissue samples with various clinicopathologic features; SGC-7901, MGC-803, BGC-823 and MKN28 GC cell lines | [81] |
circCACTIN | up-regulated | miR-331-3p | Promotes GC cells migration, invasion and EMT | 32 gastric adenocarcinoma tissue samples; GES1, BGC-823, MGC-803 and SGC-7901 GC cell lines | [82] |
ciRS-7 | up-regulated | miR-7 | Promotes cancer cell proliferation | 256 GC tissue samples (102 in training cohort and 154 in validation cohort) with various clinicopathologic features; MGC-803 and HGC-27 GC cell lines | [83] |
circHIPK3 | up-regulated | miR-124 miR-29b | Promotes cancer cell proliferation | 63 GC tissue samples (28 infiltrative type samples and 35 expanding type samples); XGC-1 (infiltrative type) and XGC-2 (expanding type) GC cell lines | [73] |
circPDSS1 | up-regulated | miR-186-5p | Promotes cell cycle and proliferation, inhibits cell apoptosis | 20 GC tissue samples; MGC-803, HGC-27, and BGC-823 GC cell lines | [84] |
circFAT1 | downregulated | miR-548 g | Inhibits cancer cell proliferation, invasion and migration | 38 GC tissue samples with various clinicopathologic features; AGS,SGC-7901, BGC-823, MKN-28, MGC-803 and MKN-45 GC cell lines | [71] |
circNF1 | up-regulated | miR-16 | Promotes cancer cell proliferation | 23 GC tissue samples with various clinicopathologic features; MKN-28, NCI-N87, AGS, KATOIII, RF1, RF-48 GC cell lines | [85] |
circYAP1 | downregulated | miR-367-5p | Tumor suppressor, inhibits cell growth and invasion | 80 GC tissue samples of various stages (13 of stage I, 25 of stage II, 38 with stage III and 4 of stage IV); HGC-27 GC cell line | [86] |
hsa_circ_0000993 | downregulated | miR-214-5p | Inhibits cellular migration, invasion and proliferation | Male patients tissue samples with stage III A primary GC (aged 59, 67 and 69 years, respectively); SGC-7901 and BGC-823 GC cell lines | [87] |
circ-ZFR | downregulated | miR-107 miR-130a | Inhibits GC cell propagation, cell cycle and promotes apoptosis | 48 GC tissue samples; AGS, AZ521, and HGC-27 GC cell lines | [88] |
circHECTD1 | up-regulated | miR-1256 | Promotes glutaminolysis, proliferation, migration, and invasion of cancer cells; promotes autophagy; potential therapeutic target | GC tissue samples with various clinicopathologic features; BGC-823, MKN-45, HGC-27, AGS, MGC-803, and SGC-7901 GC cell lines | [89] |
ciRS-133 | up-regulated | miR-133 | Aggravates tumour cachexia | Tissue and plasma samples of GC patients; SGC-7901 GC cell line | [90] |
circAKT3 | up-regulated* | miR-198 | Enhances resistance to Cisplatin chemotherapy; therapeutic target | 149 GC tissue samples (patients received CDDP treatment with/ without tumor relapse); SGC-7901 and BGC-823 GC cell lines and their CDDP-resistant strains SGC-7901CDDP and BGC-823CDDP | [91] |
Expression of circRNAs in GC
CircRNAs and the proliferation and progression of GC
CircRNAs as diagnostic and prognostic biomarkers in GC
Name | Dysregulation | Function | Sensitivity | Specificity | Cut-off value (ΔCt) | AUC | Clinicopathological association | Ref. |
---|---|---|---|---|---|---|---|---|
circPVT1 | up-regulated | Independent prognostic indicator; | – | – | – | 0.605 | Tumor stage and overall survival time | [75] |
hsa_circ_0014717 | downregulated | Diagnostic biomarker | 59.38% | 81.25% | 12.14 | 0.696 | Tumor stage, distal metastasis, CEA, and CA19–9 | [92] |
circLARP4 | downregulated | Independent prognostic indicator | 67.4% | 67.6% | 20.37 | 0.64 | Tumor size and lymphatic metastasis | [96] |
circ-KIAA1244 | downregulated | Independent prognostic indicator | 77.42% | 68.00% | 1.443 | 0.748 | TNM stage, lymphatic metastasis and overall survival time | [99] |
hsa_circ_0000467 | up-regulated | Independent prognostic factor; potential target | 70.5% | 64.8% | – | 0.799 | Lymphatic invasion, and TNM stage | [100] |
hsa_circ_0000190 | downregulated | Diagnosis biomarker | 72.1% | 68.3% | 6.83 | 0.75 | Tumor size, lymphatic metastasis, distal metastasis, TNM stage and CA19–9 | [101] |
hsa_circ_002059 | downregulated | Diagnosis biomarker | 81% | 62% | 12.9 | 0.73 | TNM stage, distal metastasis, gender and age | [102] |
hsa_circ_0000181 | downregulated | Diagnosis biomarker | 20.6% | 99% | 7.27 | 0.582 | Differentiation and CEA (plasma) | [103] |
85.2% | 53.9% | 9.4 | 0.756 | Tumor diameter, lymphatic metastasis, distal metastasis and CA19–9 (tissue) | ||||
hsa_circ_0000096 | downregulated | Diagnosis biomarker | – | – | 12.9 | 0.82 | Gender, invasion and TNM stage | [104] |
hsa_circ_0003159 | downregulated | Diagnosis biomarker | 85.2% | 56.5% | 12.31 | 0.75 | Gender, TNM stage and distal metastasis | [105] |
circPSMC3 | downregulated | Diagnosis and prognosis biomarker | 85.85% | 95.24% | 9.965 | 0.933 | TNM stage and lymphatic metastasis | [95] |
hsa_circ_0000745 | downregulated | Diagnosis biomarker | 85.5% | 45% | – | 0.683 | TNM stage (plasma) and tumor differentiation (tissue) | [106] |
hsa_circ_0006633 | downregulated | Diagnosis biomarker | 60% | 81% | 8.17 | 0.741 | Distal metastasis and CEA | [107] |
hsa_circ_0001649 | downregulated | Independent prognostic indicator and diagnosis biomarker | 71.1% | 81.6% | 0.227 | 0.834 | Tumor differentiation | [108] |
hsa_circ_0001895 | downregulated | Prognosis biomarker | 67.8% | 85.7% | 9.53 | 0.792 | Cell differentiation, Borrmann type, and CEA | [109] |
has_circ_0074362 | downregulated | Diagnosis biomarker | 84.3% | 36.2% | 12.17 | 0.63 | Lymphatic metastasis and CA19–9 | [110] |
hsa_circ_102958 | up-regulated | Diagnosis biomarker | 61% | 86% | – | 0.74 | TNM stage | [111] |
has_circ_0066444 | up-regulated | Diagnosis biomarker | 70.75% | 68.87% | – | 0.733 | Lymph metastasis | [112] |
Therapeutic potential of circRNAs in GC
Potential anti-cancer effects of circRNAs
GC therapy targeting circRNAs
Methods for circRNA identification and representation
Identification tools for circRNAs
Online resources
Database | URL | Annotation | Ref. |
---|---|---|---|
circBase | http://www.circbase.org/ | A circRNA database contains circRNA information from multiple species. | [38] |
circRNABase | Views the predicted miRNA-circRNA interactions by scanning circRNA sequences overlapping with CLIP-Seq peak. | [134] | |
Circ2Traits | http://gyanxet-beta.com/circdb/ | A database of circular RNAs that may be associated with disease and traits. Predicts the interaction between miRNAs and genes, lncRNAs, and circRNAs. | [135] |
CircInteractome | http://circinteractome.nia.nih.gov/ | Predicts binding sites of proteins to circRNAs. Predicts potential binding sites for miRNAs-circRNAs interaction. | [136] |
CircNet | New circRNA predictions and genome annotations performed using 464 RNA sequencing data. | [137] | |
Deepbase | http://deepbase.sysu.edu.cn/ | Collects 18,000 small RNAs, 36,0000 lncRNAs and 100,000 circRNA genes (human, murine, fruit flies, nematodes, etc.). | [138] |
circRNADb | http://reprod.njmu.edu.cn/circrnadb | The first database that summarises circRNAs that encode proteins. A total of 32,914 human exon circRNAs were collected. | [139] |
CIRCpedia | Constructs by using CIRCexplorer2 for bioinformatic predictive analysis of circRNAs in tissues and cell lines. | [140] | |
CSCD | http://gb.whu.edu.cn/CSCD | Collects circRNAs from tumour cell lines and normal cells from ENCODE. Predicts cellular localisation of circRNAs, MRE, RBP and variable splicing of related genes. | [141] |
circlncRNAnet | http://app.cgu.edu.tw/circlnc/ | Allows for a personalised analysis of lncRNAs, including lncRNA expression maps, gene function enrichment analysis maps, RBP-RNA network maps and miRNA network maps. | [142] |
circRNA disease | http://cgga.org.cn:9091/circRNADisease/ | CircRNA records include circRNA basic information, related disease information, circBase links and PubMed links. | [143] |