Table 1 Known circRNA-protein interactions classified by manners of action

Altering interactionsbetween proteins

circFoxo3

p53, MDM2

induce mutant p53 ubiquitination

pro-apoptosis

P

[92]

circFoxo3

p21, CDK2

dampen the activity and accessibility of CDK2

cell cycle arrest in G1 phase

P

[93]

circNfix

YBX1, Nedd4l

induce YBX1 ubiquitination and inhibit its nucleartranslocation

cell cycle arrest, anti-angiogenesis,anti-regeneration

U

[25]

circADD3

CDK1, EZH2

phosphorylate EZH2 and induce its ubiquitination

anti-metastasis

P

[94]

circAmotl1

PDK1, AKT

phosphorylate AKT and promote pAKT nucleartranslocation

anti-apoptosis, cardio-protection

P

[95]

circGLI1

p70S6K2, GSK3β

phosphorylate GSK3β

pro-metastasis

P

[96]

circCTNNB1

DDX3, YY1

transactivate YY1

tumor progression

P

[97]

circCUX1

EWSR1, MAZ

transactivate MAZ

pro-Warburg effect, tumor progression

P

[98]

circACC1

β and γ subunits of AMPK

stabilize and activate AMPK

metabolic reprogramming

N

[99]

circCcnb1

H2AX, (wild-type p53)

free Bclaf1 from p53

cell survival

P

[100]

circCcnb1

H2AX, (Bclaf1)

wrap Bclaf1 by H2AX

cell death

N

[100]

circCcnb1

Ccnb1, CDK1

deactivate Ccnb1 and retain it in the cytoplasm

cell cycle arrest in G2 phase

N

[101]

Blocking proteinsfrom DNA

circHuR

CNBP

sequester CNBP from the HuR promoter

tumor suppression

N

[102]

circSCMH1

MeCP2

tether MeCP2 and relieve its repression upon thetarget gene transcription

neuroprotection post stroke

P

[103]

circSamd4

PURA, PURB

tether PURA/B and relieve their repression uponMHC transcription

pro-myogenesis

U

[104]

ACR

DNMT3B

tether DNMT3B and decrease the methylation of thePink1 promoter

anti-autophagy

U

[105]

cia-cGAS

cGAS

block cGAS from self-DNA and inhibit its enzymatic activity

maintaining HSCs quiescent

U

[106]

Blocking proteinsfrom RNA

circSMARCA5

SRSF1

tether SRSF1 and suppress its splicing activity (SRSF3, PTBP1)

anti-migration

N

[107]

circSMARCA5

SRSF1

tether SRSF1 and suppress its splicing activity (VEGFA)

anti-angiogenesis

N

[108]

circPABPN1

HuR

sequester HuR and destabilize PABPN1 mRNA

anti-proliferation

N

[109]

circPABPN1

HuR

sequester HuR and destabilize Atg16L1 mRNA

anti-autophagy

U

[110]

circZKSCAN1

FMRP

sequester FMRP from combing with CCAR1 mRNA

anti-stemness, tumor quiescence

U

[111]

circMTO1

TRAF4

deactivate Eg5 translation

chemosensitization

U

[112]

circMMP9

AUF1

relieve the inhibition of MMP9 mRNA

pro-metastasis

P

[113]

circANRIL

PES1

prevent pre-rRNA maturation and impair ribosome biogenesis

anti-atherosclerosis

N

[114]

circPPM1F

HuR

sequester HuR and destabilize PPM1F mRNA

M1 macrophage activation

N

[115]

Blocking proteinsfrom proteins

circGSK3β

GSK3β

block GSK3β from β-catenin

pro-metastasis

N

[116]

CDR1as

p53

block p53 from MDM2

tumor suppression

U

[22]

circ102171

CTNNBIP1

block CTNNBIP1 from β-catenin

tumor progression

U

[117]

circH19

PTBP1

tether PTBP1 and inhibit its ability to cleave and activate SREBP1

adipogenesis

U

[118]

circECE1

c-myc

block c-myc from SPOP

pro-Warburg effect

P

[119]

SCAR

ATP5B

block mPTP from CypD

anti-metaflammation

U

[50]

Recruiting transcriptionfactors to chromatin

circRHOT1

TIP60

recruit TIP60 to the NR2F6 promoter and initiate transcription

tumor progression

P

[47]

circAnks1a

YBX1

recruit YBX1 to the VEGFB promoter and activate transcription

central sensitization, painbehavioral hypersensitivity

U

[120]

circ0005276

FUS

recruit FUS to the XIAP promoter

tumor progression

P

[121]

circPOK

ILF2/3 complex

potentiate the affinity of ILF2/3 to the IL-6 promoter

pro-angiogenesis

N

[122]

Recruiting modifyingenzymes to chromatin

circFECR1

TET1

induce demethylation and activate FLI1 transcription

pro-tumorigenesis

P

[123]

circMRPS35

KAT7

induce the acetylation of H4K5 and activate FOXO1/3a transcription

tumor suppression

U

[124]

circAGFG1

EZH2

induce H3K27me3 of the p53 promoter

tumor progression

U

[125]

circLRP6

LSD1, EZH2

induce H3K27me3 and H3K4me2 of the KLF2 and APC promoter

tumor progression

P

[126]

Recruiting chromatinremodelers

circDONSON

NURF complex

recruit the NURF complex to the SOX4 promoter and activate itstranscription

tumor progression

U

[127]

circKcnt2

NuRD complex

recruit the NuRD complex to the Batf promoter and inhibit itstranscription

anti-inflammation

U

[128]

Ternary complexesregulating RNA stability

circNSUN2

IGF2BP2, (HMGA2 mRNA)

stabilize HMGA2 mRNA

pro-metastasis

P

[43]

circPOK

ILF2/3, (mRNA of IL-6 andVEGF)

stabilize the mRNA of IL-6 and VEGF

tumor progression, pro-angiogenesis

N

[122]

circFNDC3B

IGF2BP3, (CD44 mRNA)

stabilize CD44 mRNA

tumor progression

P

[129]

Ternary complexesregulating translation

circMALAT1

Ribosome, (PAX5 mRNA)

retard PAX5 translation

self-renewal of HCC stem cells

U

[130]

circYap

eIF4G, PABP, (Yap mRNA)

interrupt the assembly of Yap translation initiation machinery

tumor suppression

N

[131]

circMYBL2

PTBP1, (FLT3 mRNA)

promote FLT3 translation

AML progression

P

[132]

Translocating proteinsto the nucleus

circAmotl1

c-myc

retain c-myc in the nucleus and increase its affinity to targets

pro-tumorigenesis

P

[46]

circAmotl1

STAT3

facilitate the nuclear translocation of STAT3

pro-wound repair

P

[133]

circDNMT1

p53, AUF1

facilitate the nuclear translocation of p53 and AUF1, elevatingLC3B level and stabilizing DNMT1 mRNA, respectively

pro-autophagy, anti-senescence,tumor progression

P

[134]

circABCC1

β-catenin

redistribute β-catenin

tumor progression

U

[135]

circSOX4

β-catenin

translocate β-catenin to the nucleus

tumor progression

P

[136]

Translocating proteinsto the cytoplasm

circFoxo3

ID-1, E2F1, FAK, HIF1α

retain these proteins in the cytoplasm and arrest their functions

pro-senescence

P

[137]

circFOXP1

PTBP1

translocate PTBP1 to the cytoplasm and stabilize PKLR mRNA

pro-Warburg effect, tumor progression

N

[138]

circSTAG1

ALKBH5

retain ALKBH5 in the cytoplasm

anti-depression

U

[139]

circBACH1

HuR

translocate HuR to the cytoplasm

cell cycle progression

P

[140]

circZFP609

HIF1α

retain HIF1α in the cytoplasm

anti-angiogenesis

U

[141]

circCCAC1

EZH2

retain EZH2 in the cytoplasm

pro-metastasis

P

[24]

Other regions

circERBB2

PA2G4

translocate PA2G4 to the nucleolus and promote rDNA transcription

tumor progression

P

[142]

circSKA3

Tks5, Integrin β1

recruit Tks5 to the membrane and co-localize with integrin β1;induce the formation of invadopodia

pro-invasion, pro-metastasis

P

[143]

mecciND1, mecciND5

RPA32, hnRNPA1, TOM40

interact with TOM40 and facilitate the mitochondrial importationof RPA32 and hnRNPA1, respectively

metabolism of mtDNA and mtRNA;not clear

U

[143]

mecciRNAs

PNPASE

control the mitochondrial importation of mecciRNAs

not clear

U

[52]

Unknown orunconfirmedmanners

circ0011460

PGT

just verify the interaction by RIP; increase PGT level

positive correlation with pre-eclampsia

P

[144]

circ0075932

PUM2

just verify the interaction by RNA pull-down; increase PUM2 level

pro-inflammation, pro-apoptosis

U

[145]

circFndc3b

FUS

just verify the interaction by RIP; decrease FUS level

pro-angiogenesis, anti-apoptosis

P

[146]

circZNF292

LDHA

just verify the interaction by RIP; increase LDHA level

pro-glycolysis

N

[147]

circAmotl1

pAKT

just verify the interaction by RIP; activate AKT pathway

chemoresistance

P

[148]

circ0075804 (circE2F3)

HNRNPK

stabilize E2F3 mRNA; the formation of ternary complex is notconfirmed

pro-proliferation, anti-apoptosis

P

[149]

circPTK2

vimentin

just verify the interaction by RNA pull-down

tumor progression

U

[150]

circ406961

ILF2

just verify the interaction by RNA pull-down; decrease ILF2 leveland suppress the STAT3/JNK pathway

anti-inflammation (induced by PM_2.5)

U

[151]

circBbs9

Ccnd2

just verify the interaction by RIP; increase Ccnd2 level

pro-proliferation

U

[152]

circHECTD1

ZC3H12A

reduce ZC3H12A ubiquitination by attenuatinginteraction between ZC3H12A and HECTD1; this study only showscircHECTD1 negatively correlates with HECTD1

deactivation and pro-apoptosis ofalveolar macrophage activated bysilica

N

[153]

circFOXK2

YBX1, hnRNPK

enhance the interaction of YBX1 and hnRNPK with NUF2 andPDXK; lack a detailed mechanism

tumor progression

N

[154]

circMUC16

ATG13

just verify the interaction by RNA pull-down; increase ATG13 level

pro-autophagy

P

[155]

circUBR5

QKI, NOVA1 (U1 snRNA)

probably participate in RNA splicing; lack a detailed mechanism

non-functional phenotype

U

[156]

circNF1–419

Dynamin-1, Adaptor protein2 B1 (AP2B1)

just verify the interaction by RNA pull-down and RIP; lack a detailed mechanism

pro-autophagy, senile dementiadelay

U

[157]

circNOL10

SCML1

just verify the interaction by RNA pull-down; increase SCML1 level

tumor suppression

U

[158]

circHipk3

Notch1 intracellular domain(N1ICD)

verify the interaction by RNA pull-down and RIP; increase N1ICDexpression, stability, acetylation; lack a detailed mechanism

cardiac regeneration

U

[159]

cIARS

ALKBH5

inhibit the ALKBH5-mediated interaction between Beclin1 andBcl-2; lack a detailed mechanism

pro-autophagy, pro-ferroptosis

U

[160]