Table 3.
LncRNAs regulating Treg cells during homeostasis and cancer.
| LncRNA | LncRNA type | Molecular Interaction | Cancer type | T cell subset | Species | Affected Signaling Molecules/Pathway | Function | Ref. |
|---|---|---|---|---|---|---|---|---|
| FENDRR | intergenic | lncRNA- RNA | HCC | Treg cells | h, m | miR-423- 5p/GADD45B | FENDRR binds to miR-423-5p and upregulates GADD45B. This decreases production of TGF-β and IL-10 by Treg cells, thereby preventing Treg-driven immune evasion in HCC. | (129) |
| Flatr | intronic | – | – | Treg cells | m | FoxP3 | Flatr promotes the expression of FoxP3 and enhances the immunosuppressive function of Tregs. | (125) |
| Flicr | intergenic | – | – | Treg cells | h, m | FoxP3 | Flicr inhibits the expression of FoxP3 by modifying chromatin accessibility and limits the immunosuppressive function of Tregs. | (126) |
| linc- POU3F3 | intergenic | lncRNA- protein | GC | Treg cells | h | TGF-β/SMAD2/3 | Linc-POU3F3 promotes Treg cell proliferation by binding TGF-β and inducing TGF-β/SMAD signaling in gastric cancer. | (130) |
| lnc-EGFR | antisense | lncRNA- protein | HCC | Treg cells | h | EGFR, AP-1/ NFAT1/FoxP3 axis |
Lnc-EGFR promotes Treg cell differentiation by inhibiting EGFR ubiquitination via c-CBL and subsequent degradation. This amplifies downstream signaling via AP-1 and NFAT1. | (93) |
| lnc-INSR | intergenic | lncRNA- protein | PALL | Treg cells | h | INSR/PI3K/Akt | Lnc-INSR binds to INSR and abnormally activates INSR and PI3K/Akt signaling, thereby enhancing Treg cell differentiation and reducing cytotoxic T cells in PALL. | (131) |
| lnc-Smad3 | sense | lncRNA- protein | – | Treg cells | m | TGF-β/Smad3/ HDAC1/ Ash1l | Lnc-Smad3 blocks Smad3 transcription via deacetylation by HDAC1. TGF-β mediated activation of Smad3 represses lnc-Smad3 allowing Ash1l to induce H3K4me3 at Smad3 and FoxP3 promoters to promote iTreg polarization. | (127) |
| MIAT | intergenic | – | HCC | Treg cells, CD8+ T cells | h, m | PD-1/CTLA4 | LncRNA MIAT correlates with Tregs and exhausted CD8+ T cells expressing the co-inhibitory receptors PD-1 and CTLA-4 in HCC. | (75) |
| PVT1 | intergenic, sense | lncRNA- protein | – | Treg cells | h, m | PVT1/Myc | In CD4+ T cells of Sjörgen’s disease patients, highly expressed lncRNA PVT1 regulates Myc expression, thereby affecting T cell proliferation and effector function. | (128) |
| RP11- 323N12.5 | sense | lncRNA- protein | GC | Treg cells | h | c-MYC/YAP1 | RP11-323N12.5 induces expression of the transcription factor YAP1, which promotes Treg cell differentiation and GC growth. | (132) |
| SNHG1 | intergenic | lncRNA- RNA | BC | Treg cells | h | miR-488/IDO | LncRNA SNHG1 inhibits Treg cell differentiation via regulating miR-488/IDO resulting in tumor immune escape. | (133) |
BC, breast cancer; GC, gastric cancer; HCC, hepatocellular carcinoma; PALL, pediatric acute lymphoblastic leukemia; h, human; m, mouse.