Table 1.
Role of circRNAs in DM and associated complications.
| Disease | CircRNA | Expression level | Finding | References |
|---|---|---|---|---|
| T1DM | CircARHGAP12 | Down | May be a potential biomarker for T1DM | (5) |
| CircRNA 000286 | Down | May participate in proinflammatory cytokine-mediated β-cell dysfunction | (35) | |
| CircRNA 017277 | Down | May participate in proinflammatory cytokine-mediated β-cell dysfunction | (35) | |
| Hsa_circ_0060450 | Up | Functions as a sponge of miR-199a-5p to restrain the JAK-STAT signaling pathway and further inhibit macrophage-mediated inflammation | (36) | |
| CircPPM1F | Up | Regulates M1 macrophage activation via the circPPM1F−HuR−PPM1F−NF-κB axis | (37) | |
| Hsa_circ_0002202 | Up | Mediates IFN-I-induced macrophage inflammation | (38) | |
| Hsa_circ_0002473 | Up | Associates with a pro-apoptotic feedback loop in β-cells | (39) | |
| Hsa_circ_0072697 | Down | May mediate the risk for T1DM via the circ_0072697−miR-15a−UBASH3A network | (40, 41) | |
| T2DM | CircHIPK3 | Down Up |
Regulates the expression level of pivotal β-cell genes in rats May function as a potential biomarker for the diagnosis of T2DM in patients |
(5) (42) |
| CiRS-7 | Down Up |
Silencing ciRS-7 diminishes prolactin-stimulated proliferation of primary rat β-cells May function as a potential biomarker for the diagnosis of T2DM in patients |
(5) (42) |
|
| Rno_circRNA_008565 | Down | Binds with rno-miR-504 to influence autophagy of rat islet β-cells | (43) | |
| Circ-Tulp4 | Down | Regulates β-cell proliferation via miR-7222-3p−soat1−cyclin D1 signaling | (44) | |
| Novel_circ_0016196 | Down | Interacts with miR-877-3p and modulates mitochondrial apoptosis | (45) | |
| Novel_circ_0016198 | Down | Interacts with miR-877-3p and modulates mitochondrial apoptosis | (45) | |
| Novel_circ_0005686 | Down | Interacts with miR-877-3p and modulates mitochondrial apoptosis | (45) | |
| Hsa_circ_0002590 | Up | Interacts with miR-149-5p and inhibits insulin secretion | (45) | |
| Novel_circ_000372 | Up | Interacts with miR-149-5p and inhibits insulin secretion | (45) | |
| Hsa-circRNA11783-2 | Down | May be a sponge for miR-608 and miR-3907 | (46) | |
| Circ_CCNB1 | Up | May be related to the progression of T2DM and may function as a potential biomarker for the diagnosis of T2DM | (47) | |
| Circ_0009024 | Down | May be related to the progression of T2DM and may function as a potential biomarker for the diagnosis of T2DM | (47) | |
| Hsa_circ_0071106 | Up | May be used as a diagnostic marker for T2DM | (48) | |
| Hsa_circ_0063425 | Down | Binds with miR-19a-3p and is positively related to AKT | (49) | |
| Hsa_circ_0056891 | Down | Binds with miR-1-3p and is positively related to PI3K | (49) | |
| CircGlis3 | Up | Impairs β-cell function under lipotoxic conditions and may be a potential biomarker for T2DM | (50) | |
| CircANKRD36 | Up | Correlates with chronic inflammation in T2DM; silencing of circANKRD36 suppresses insulin resistance and inflammation by targeting miR-145 via XBP1 | (51, 52) | |
| Hsa_circ_0054633 | Up | May be used as a marker for T2DM | (53, 54) | |
| GDM | Circ_0008285 | Up | Correlates with total cholesterol | (55) |
| Circ_0001173 | Down | Correlates with glycated hemoglobin | (55) | |
| Hsa_circ_102682 | Down | Is valuable for diagnosis of GDM | (56) | |
| CircVEGFC | Up | Has high sensitivity and specificity in early diagnosis of GDM and is positively related to fetal malformations and hypertension | (57) | |
| CircACTR2 | Up | Is related to higher rates of premature delivery, miscarriage, intrauterine death, fetal malformation, intrauterine infection, and hypertension, but is not associated with macrosomia and intrauterine distress | (58) | |
| Hsa_circRNA_0039480 | Up | Has a diagnostic value in the first, second, and third trimesters of pregnancy | (59) | |
| Circ-PNPT1 | Up | Facilitates HG-induced biological dysfunction in trophoblasts cell via the miR-889-3p−PAK1 axis | (60) | |
| Hsa_circ_0005243 | Down | Mediates trophoblast dysfunction and inflammation by regulating the β-catenin and NF-κB signaling pathways | (61) | |
| Circ_0074673 | Up | Regulates the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200−MEOX2 axis | (62) | |
| Hsa_circ_0054633 | Up | Is useful for GDM diagnosis and plays a role in the regulation of β-cell proliferation and glucose metabolism | (63, 64) | |
| Hsa_circRNA_102893 | Down | Is valuable for diagnosis of GDM | (65, 66) | |
| DR | Circ-ITCH | Down | Modulates angiogenesis by sponging miR-22 | (67) |
| Hsa_circ_0002570 | UP | Promotes angiogenesis and inflammation in hRMECs via the circ_0002570−miR-1243−angiomotin axis | (68) | |
| Circ_0005015 | UP | Facilitates angiogenesis by the circ_0005015−miR-519d-3p−MMP-2/XIAP/STAT3 pathway | (69) | |
| Hsa_circ_0081108 | UP | Facilitates angiogenesis by the hsa_circ_0081108−miR-29b−VEGF axis | (70) | |
| Circular RNA-ZNF609 | UP | Facilitates angiogenesis by the miR-615-5p−MEF2A pathway | (71) | |
| Mmu_circ_0000254 | Up | Mediates retinal vascular dysfunction and functions as a sponge of miR-579 | (72) | |
| CircDNMT3B | Down | Mediates vascular dysfunction in diabetic retinas by the circDNMT3B−miR-20b-5p−BAMBI axis | (73) | |
| Circular RNA-ZNF532 | UP | Regulates DM-induced retinal pericyte degeneration by sponging miR-29a-3p | (74) | |
| Hsa_circRNA_063981 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_404457 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_100750 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_406918 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_104387 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_103410 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circRNA_100192 | Up | May be a potential biomarker for DR | (75) | |
| Hsa_circ_0001953 | Up | Has a diagnostic value in PDR patients | (76) | |
| CircEhmt1 | Up | Reduces HG-induced apoptosis and inflammation via the NFIA/NLRP3 pathway | (77) | |
| Hsa_circ_0041795 | UP | Promotes HG-triggered cell apoptosis via the miR-646−VEGFC pathway | (78) | |
| CircRNA_0084043 | UP | Promotes HG-triggered cell apoptosis via the circRNA_0084043−miR-140-3p−TGFA axis | (79) | |
| Circ_001209 | UP | Promotes HG-triggered cell apoptosis via the miR-15b-5p−COL12A1 axis | (80) | |
| Circ-PSEN1 | UP | Mediates ferroptosis of HG-treated retinal pigment epithelial cells via the miR-200b-3p−cofilin-2 axis | (81) | |
| CircHIPK3 | Down | Mediates retinal vascular dysfunction via the circHIPK3−miR-30a-3p−VEGFC/WNT2/FZD4 axis | (82, 83) | |
| DN | Circ_0123996 | Up | Facilitates fibrosis by sponging miR-149-5p | (84) |
| CircEIF4G2 | Up | Facilitates fibrosis via the circEIF4G2−miR-218−SERBP1 pathway | (85) | |
| CircRNA_15698 | Up | Facilitates fibrosis via the circRNA_15698−miR‐185−TGF‐β1 axis | (86) | |
| Circ_0000491 | Up | Facilitates fibrosis via the circRNA_0000491−miR‐101b−TGFβRI axis | (87) | |
| CircLRP6 | Up | Mediates mesangial cell dysfunction via the circLRP6−miR‐205−HMGB1−TLR4/NF‐κB regulatory network | (88) | |
| CircHIPK3 | Up | Promotes cell proliferation and fibrosis by sponging miR-185 | (89) | |
| Circ_DLGAP4 | Up | Promotes cell proliferation and fibrosis via the circ_DLGAP4−miR-143−ERBB3/NF-κB/MMP-2 axis | (90) | |
| Hsa_circ_0125310 | Up | Promotes cell proliferation and fibrosis via the circ_0125310−miR‐422a−IGF1R-p38 axis | (91) | |
| CircACTR2 | Up | Promotes inflammation and fibrosis in HK-2 cells | (92) | |
| Circ-FBXW12 | Up | Promotes human mesangial cell inflammation and ECM accumulation via the miR-31-5p−LIN28B axis | (93) | |
| Hsa_circ_0004442 | Up | Promotes human mesangial cell inflammation and ECM accumulation via the hsa_circ_0004442−miR-126-5p/miR-204-5p−AKT/NF-κB pathway | (94) | |
| Circ_0080425 | Up | Inhibits cell proliferation and fibrosis via the circ_0080425−miR-24-3p−FGF11 axis | (95) | |
| Circ_LARP4 | Down | Inhibits cell proliferation and fibrosis by sponging miR-424 | (96) | |
| Circ-AKT3 | Down | Inhibits fibrosis via the circ-AKT3−miR-296-3p−E-cadherin pathway | (97) | |
| CircSMAD4 | Down | Inhibits fibrosis via the circSMAD4−miR-377-3p−BMP7 pathway | (98) | |
| Circ-ITCH | Down | Alleviates renal inflammation and fibrosis in STZ-induced diabetic mice by regulating the miR-33a-5p−SIRT6 axis | (99) | |
| CircRNA_010383 | Down | Knockdown facilitates proteinuria and renal fibrosis in DN; is a sponge for miRNA-135a | (100) | |
| Hsa_circ_0003928 | Up | Regulates HG-induced inflammation via the miR-151-3p−Anxa2 axis | (101) | |
| Hsa_circRNA_102682 | Down | May be relevant to the pathogenesis of hyperhomocysteinemia in DN and may be a potential biomarker for DN | (102) | |
| Circ_0000712 | Up | Promotes apoptosis via the circ_0000712−miR-879-5p−SOX6 axis | (103) | |
| Circ_WBSCR17 | Up | Promotes apoptosis via the miR-185-5p−SOX6 regulatory axis | (104) | |
| Circ_0000285 | Up | Promotes apoptosis via the circ_0000285−miR-654-3p−MAPK6 axis | (105) | |
| Mmu_circRNA_0000309 | Down | Is involved in germacrone-mediated improvement of DN via the miR-188-3p−GPX4 axis | (106) | |
| Circ_0037128 | Up | Promotes cell proliferation and fibrosis via the circ_0037128−miR-17-3p−AKT3 axis; promotes inflammation and fibrosis in HK-2 cells via the circ_0037128−microRNA-497-5p−NFAT5 axis | (107, 108) | |
| Circ_0000064 | Up | Promotes cell proliferation and fibrosis by sponging miR-143; is involved in emodin-mediated alleviation of DN via the circ_0000064 −miR-30c-5p−Lmp7 axis | (109, 110) | |
| DC | CircRNA11783-2 | Down | May be correlated with DC | (46) |
| CircRNA_000203 | Up | Promotes myocardial fibrosis via the circRNA_000203−miR-26b-5p−Col1a2/CTGF axis | (111) | |
| CircRNA_010567 | Up | Promotes myocardial fibrosis via the circRNA_010567−miR-141−TGF-β1 axis | (112) | |
| CircHIPK3 | Up | Promotes myocardial fibrosis via the circHIPK3−miR-29b-3p−Col1a1−Col3a1 axis | (113) | |
| Hsa_circ_0076631 | Up | Promotes an inflammatory response and pyroptosis via the hsa_circ_0076631−miR-214-3p−caspase-1 axis | (114) | |
| Circ_0071269 | Up | Promotes an inflammatory response and pyroptosis via the microRNA-145−gasdermin A axis | (115) | |
| DF | Hsa_circ_0084443 | Up | Modulates keratinocyte migration via the PI3K, EGFR, and ERK signaling pathways | (116) |
| Hsa_circ_0000907 | Up | May function as a novel biomarker for early diagnosis of DFU | (117) | |
| Hsa_circ_0057362 | Up | May function as a novel biomarker for early diagnosis of DFU | (117) | |
| CircRNA_072697 | Up | May be a new target for the treatment of DFU | (118, 119) | |
| Diabetic neuropathy | CircHIPK3 | Up | Functions as a sponge for miR-124, and silencing this circRNA eases mechanical hyperalgesia and thermal hyperalgesia | (120) |