# Functional roles and mechanisms of circRNA-protein interactions in cancer progression and tumor immune regulation

**Authors:** Lin Yang, Chunhong Li, Xiulin Jiang, Yixiao Yuan, Chongxin Li, Qiang Zhou, Qiang Wang, Jie Xiong

PMC · DOI: 10.3389/fimmu.2026.1771949 · Frontiers in Immunology · 2026-02-11

## TL;DR

This paper explores how circular RNAs interact with proteins to influence cancer growth and immune responses, offering new ways to diagnose and treat cancer.

## Contribution

The paper highlights the novel functional roles of circRNA–protein interactions in tumor progression and immune regulation.

## Key findings

- circRNA–protein interactions modulate protein stability, activity, and localization in cancer cells.
- These interactions influence tumor progression through proliferation, metastasis, and immune evasion.
- Understanding these mechanisms provides new insights for cancer diagnosis and therapy.

## Abstract

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs characterized by covalently closed loop structures, which confer high stability and evolutionary conservation. Beyond their well-known role as microRNA sponges, circRNAs can directly interact with proteins to modulate protein stability, activity, subcellular localization, and transcriptional or epigenetic regulation. These circRNA–protein interactions play critical roles in cancer progression by influencing tumor cell proliferation, metastasis, stemness, metabolic reprogramming, cell death, and therapy resistance. Moreover, they can shape the tumor immune microenvironment, affecting immune cell infiltration, immune evasion, and responses to immunotherapy. Understanding the mechanisms and functional consequences of circRNA–protein interactions provides new insights into tumor biology and offers promising avenues for cancer diagnosis, prognosis, and therapeutic intervention.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], ITGA5 (integrin subunit alpha 5) [NCBI Gene 3678] {aka CD49e, FNRA, VLA-5, VLA5A}, MIR671 (microRNA 671) [NCBI Gene 768213] {aka MIRN671, hsa-mir-671, mir-671}, RBM4 (RNA binding motif protein 4) [NCBI Gene 5936] {aka LARK, RBM4A, ZCCHC21, ZCRB3A}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, RBM45 (RNA binding motif protein 45) [NCBI Gene 129831] {aka DRB1, RB-1}, MIR1275 (microRNA 1275) [NCBI Gene 100302123] {aka MIRN1275, hsa-mir-1275, mir-1275}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, LDHA (lactate dehydrogenase A) [NCBI Gene 3939] {aka GSD11, HEL-S-133P, LDHM, PIG19}, SRSF1 (serine and arginine rich splicing factor 1) [NCBI Gene 6426] {aka ASF, NEDFBA, SF2, SF2p33, SFRS1, SRp30a}, RBP4 (retinol binding protein 4) [NCBI Gene 5950] {aka MCOPCB10, RDCCAS}, TADA2A (transcriptional adaptor 2A) [NCBI Gene 6871] {aka ADA2, ADA2A, KL04P, TADA2L, hADA2}, SIRT2 (sirtuin 2) [NCBI Gene 22933] {aka SIR2, SIR2L, SIR2L2}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, LGALS9 (galectin 9) [NCBI Gene 396972] {aka UATP.I}, MIR320A (microRNA 320a) [NCBI Gene 407037] {aka MIRN320, MIRN320A, hsa-mir-320a, mir-320a}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, FTH1 (ferritin heavy chain 1) [NCBI Gene 2495] {aka FHC, FTH, FTHL6, HFE5, NBIA9, PIG15}, SLC27A2 (solute carrier family 27 member 2) [NCBI Gene 11001] {aka ACSVL1, FACVL1, FATP2, HsT17226, VLACS, VLCS}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, RBMS1 (RNA binding motif single stranded interacting protein 1) [NCBI Gene 5937] {aka C2orf12, HCC-4, MSSP, MSSP-1, MSSP-2, MSSP-3}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, NTRK1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 4914] {aka MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, BRD4 (bromodomain containing 4) [NCBI Gene 23476] {aka CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, LATS1 (large tumor suppressor kinase 1) [NCBI Gene 9113] {aka WARTS, wts}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, YTHDC1 (YTH N6-methyladenosine RNA binding protein C1) [NCBI Gene 91746] {aka YT521, YT521-B}, MIR301B (microRNA 301b) [NCBI Gene 100126318] {aka MIRN301B, mir-301b}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, EIF3H (eukaryotic translation initiation factor 3 subunit H) [NCBI Gene 8667] {aka EIF3S3, eIF3-gamma, eIF3-p40}, NUP160 (nucleoporin 160) [NCBI Gene 23279] {aka NPHS19}, NBR1 (NBR1 autophagy cargo receptor) [NCBI Gene 4077] {aka 1A1-3B, IAI3B, M17S2, MIG19}, METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, MIR661 (microRNA 661) [NCBI Gene 724031] {aka MIRN661, hsa-mir-661}, HIPK2 (homeodomain interacting protein kinase 2) [NCBI Gene 28996] {aka PRO0593}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, AKAP12 (A-kinase anchoring protein 12) [NCBI Gene 9590] {aka AKAP250, SSeCKS}, MIR326 (microRNA 326) [NCBI Gene 442900] {aka MIRN326, hsa-mir-326, mir-326}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, SDHB (succinate dehydrogenase complex iron sulfur subunit B) [NCBI Gene 6390] {aka CWS2, IP, MC2DN4, PGL4, PPGL4, SDH}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, RANBP2 (RAN binding protein 2) [NCBI Gene 5903] {aka ADANE, ANE1, IIAE3, NUP358, TRP1, TRP2}, NFIB (nuclear factor I B) [NCBI Gene 4781] {aka CTF, HMGIC/NFIB, MACID, NF-I/B, NF1-B, NFI-B}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, SPOP (speckle type BTB/POZ protein) [NCBI Gene 8405] {aka BTBD32, NEDMACE, NEDMIDF, NSDVS1, NSDVS2, TEF2}, IFNG (interferon gamma) [NCBI Gene 396991], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, TNC (tenascin C) [NCBI Gene 3371] {aka 150-225, DFNA56, GMEM, GP, HXB, JI}, CTBP2 (C-terminal binding protein 2) [NCBI Gene 1488]
- **Diseases:** CRC (MESH:D015179), pancreatic cancer (MESH:D010190), GBM (MESH:D005910), PCa (MESH:D011471), ischemia-reperfusion injury (MESH:D015427), metastases (MESH:D009362), PDAC (MESH:D021441), inflammation (MESH:D007249), ESCC (MESH:D000077277), cytotoxic (MESH:D064420), NK (MESH:D054066), Tumor (MESH:D009369), colitis (MESH:D003092), lung cancer (MESH:D008175), ovarian cancer (MESH:D010051), tumorigenesis (MESH:D063646), GC (MESH:D013274), LNM (MESH:D008207), TAM (MESH:D020914), IBD (MESH:D015212), TNBC (MESH:D064726), breast cancer (MESH:D001943), lung adenocarcinoma (MESH:D000077192), NPC (MESH:D000077274), liver tumor (MESH:D008113), hypoxia (MESH:D000860), HNSCC (MESH:D000077195), glioblastoma (MESH:D005909), bladder cancer (MESH:D001749), SCC (MESH:D002294), RCC (MESH:D002292), AML (MESH:D015470), HCC (MESH:D006528)
- **Chemicals:** doxorubicin (MESH:D004317), cisplatin (MESH:D002945), PEG (-), Norathyriol (MESH:C069053), SCH772984 (MESH:C587178), lactate (MESH:D019344), acetyl-CoA (MESH:D000105), arachidonic acid (MESH:D016718), lipid (MESH:D008055), m6A (MESH:C005955), glucose (MESH:D005947), sorafenib (MESH:D000077157), PLGA (MESH:D000077182)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12932422/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932422/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932422/full.md

---
Source: https://tomesphere.com/paper/PMC12932422