Table 2.
LncRNAs regulating CD4+ T cell subsets during homeostasis and cancer.
| LncRNA | LncRNA type | Molecular Interaction | Cancer type | T cell subset | Species | Affected Signaling Molecules/Pathway | Function | Ref. |
|---|---|---|---|---|---|---|---|---|
| CRNDE-h | intergenic, antisense | lncRNA- protein | CRC, Glioma, HCC, LC |
Th17 | h | RORγ/IL-17 | CRNDE-h is a tumor exosome-transmitted lncRNA promoting Th17 cell differentiation by inhibiting Itch-mediated ubiquitination and degradation of RORγt in CRC. | (99) |
| Dreg1 | antisense | – | – | Th2 | h, m | Dreg1/Gata3 | Dreg1 induces Gata3 expression in Th2 cells. | (100) |
| GATA3- AS1 | antisense | lncRNA- protein | – | Th2 | h | WDR5/GATA3/IL-5/ IL-4/IL-13 | GATA3-AS1, neighboring the Gata3 locus, induces Th2 lineage commitment by interacting with the methyltransferase WDR5 and inducing GATA3, IL-5 and IL-13 expression. | (101) |
| LINC00892 | intergenic, sense | – | NHL | CD4+ T cells | h, m | – | LINC00892 is induced by T cell activation and expressed in CD4+ T helper and follicular lymphoma T helper cells. | (102) |
| LINC01882 | intergenic, antisense | – | – | CD4+ T cells | h | LINC01882/ZEB1/MA P2K4 | LINC01882 is expressed in naïve CD4+ T cells. Its knockdown increased the expression of transcription factor ZEB1 and MAP2K4, both linked to IL-2 signaling. | (103) |
| linc-Ccr2- 5′AS | intergenic | – | – | Th2 | m | Ccr1/Ccr2/Ccr3/Ccr5 | Linc-Ccr2-5′AS and the transcription factor GATA3 represent a key regulatory network for Th2-specific cell differentiation and migration. | (104) |
| linc-MAF-4 | intergenic | lncRNA- DNA | – | Th1 | h | EZH2/LSD1/MAF-4 | Linc-MAF-4 modulates Th1 differentiation and function through interaction with EZH2 and LSD1 to epigenetically repress MAF. | (105) |
| Lnc-DDIT4 | – | lncRNA- protein | – | Th17 | h | Lnc-DDIT4/DDIT4/ mTOR signaling |
Lnc-DDIT4 induces DDIT4 expression, which blocks mTOR signaling and inhibits IL-17 production. | (106) |
| LncRNA- GAS5 | sense | lncRNA- protein | – | Th17 | h, m | GAS5/STAT3 | lncRNA-GAS5 inhibits Th17 differentiation by modulating STAT3. | (107) |
| lncRNA- GM | – | lncRNA- protein | – | Th17 | h, m | lncRNA-GM/Foxo1 | lncRNA-GM directly inhibits Foxo1 dephosphorylation, thus promoting IL-23R expression and Th17 differentiation. | (108) |
| NEAT1 | intergenic | lncRNA- protein | – | Th17 | h, m | NEAT1/STAT3 | NEAT1 reduces STAT3 levels, thereby blocking Th17 cell differentiation in PBMCs of rheumatoid arthritis patients. | (109) |
| NeST | intergenic, antisense | lncRNA- protein | – | CD8+ T cells, CD4+ Th1 | h, m | NeST/WDR5 | NeST binds to WDR5, a component of the H3K4 methyltransferase complex, thus increasing H3K4me3 at the IFN- γ locus in CD8+ and CD4+ Th1 cells. | (77, 78) |
| NKILA | sense | lncRNA- protein | BC, LC | Th1, CD8+ T cells |
h | Ca2+/ calmodulin/ NFκB/STAT1 |
NKILA regulates T cell sensitivity to AICD by inhibiting NFkB activity and its anti-apoptotic target genes via IkBa. | (28) |
| NNT | intergenic, antisense | – | – | CD4+ T cells | h | IFN-γ signaling | NNT is expressed in activated CD4+ T cells and is localized near the IFN-γ receptor gene, indicating a functional relationship. | (110) |
| NRON | intronic, sense | lncRNA- protein | – | CD8+ T cells, CD4+ T cells | h, m | NRON/NFAT-IQGAP- CK1-GSK3-DYRK | NRON (noncoding repressor of NFAT) regulates nuclear trafficking of NFAT via an RNA-protein scaffold complex to limit excessive T cell activation and NFAT-dependent cytokine production. | (79–81) |
| RUNX1-IT1 | intronic, antisense | lncRNA- protein | – | Th1 | h | RUNX1- IT1/p53/NrCAM |
RUNX1-IT1 regulates NrCAM through interacting with p53, thereby modulating T-bet and CXCL10 levels in Graves’ disease. | (111) |
| STAT4-AS1 | sense | lncRNA- protein | – | Th17 | h | STAT4-AS1/ROR-γt | STAT4-AS1 inhibits Th17 differentiation by binding ROR-γt and blocking its translocation to the nucleus and its binding to the IL-17 promoter. | (112) |
|
Th2-LCR
lncRNA cluster |
antisense, sense | lncRNA- DNA | Th2 | h, m | MLL/IL-4/IL-5/IL-13 | The Th2-LCR lncRNA cluster regulates through histone acetylation, (de-)methylation and chromatin remodeling the Th2 cytokine locus including IFN-γ, IL-4, IL-5 and IL-13. | (56, 113, 114) | |
| Xloc003810 | – | – | MG-T | Th17, Treg cells |
h | Xloc003810/IFN-γ/ TNF-α/IL-1β | Xloc003810 increases thymic Th17/Treg ratio and CD4+ PD1+ T cells in MG-T, which is accompanied by increased production of IFN-γ, TNF-α and IL-1β. | (115, 116) |
BC, breast cancer; CRC, colorectal cancer; HCC, hepatocellular carcinoma; LC, lung cancer; MG-T, myasthenia gravis with thymoma; NHL, non-Hodgkin B-cell lymphoma; h, human; m, mouse.