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Table 1 LncRNAs involved in TIME

From: Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

LncRNA Related immune cell Cancer type Expression Mediator miRNA Target gene/pathway Immunity-Related Mechanisms Clinical significance References
LINK-A TNBC Upregulated in tumor cells PtdIns(3,4,5)P3, GPCR, PKA, TRIM7 LINK-A-dependent downregulation of antigenicity and intrinsic tumor suppression by mediating the crosstalk between PtdIns(3,4,5)P3 and GPCR Overall survival [12]
LINC00665 HGSOC Upregulated in tumor cells FTX Influencing the infiltration level of macrophages and DCs, and inhibiting Tregs and prevent T-cell exhaustion by FTX Overall survival [10]
GNAS-AS1 Macrophages ER+ Breast cancer Upregulated in tumor cells and M2 macrophages miR-433-3p GATA3 Accelerating M2 macrophage polarization [30]
GNAS-AS1 Macrophages Non-small cell lung cancer Upregulated in tumor cells and M2 macrophages miR-4319 NECAB3 Regulating macrophage polarization Overall survival, metastasis-free survival [31]
CCAT1 Macrophages Prostate cancer Downregulated in M2 macrophages miR-148a PKCζ Regulating macrophage polarization [32]
NIFK-AS1 Macrophages Endometrial Cancer Downregulated in M2 macrophages miR-146a Notch1 Inhibiting M2 macrophage polarization [36]
XIST Macrophages Lung cancer Upregulated in M2 macrophages Regulating macrophage polarization [37]
MM2P Macrophages Upregulated in M2 macrophages STAT6 Accelerating M2 macrophage polarization [38]
ANCR Macrophages Gastric cancer Upregulated in tumor cells FoxO1 Promoting tumor metastasis through hindering M1 type differentiation of macrophages by facilitating FoxO1 ubiquitination degradation [39]
LincRNA-p21 Macrophages Breast cancer Upregulated in M2 macrophages MDM2, P53, NF-κB, STAT3 Inhibiting macrophage polarization into pro-inflammatory M1 by promoting its interaction with p53 [40]
LncRNA-cox-2 Macrophages HCC Downregulated in M2 macrophages Preventing immune evasion and metastasis of cancer by altering M1/M2 macrophage polarization [41]
MALAT1 Macrophages Thyroid cancer Upregulated in tumor cells and M2 macrophages FGF2 MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of tumor cells and induces vasculature formation [42]
SBF2-AS1 Macrophages Pancreatic cancer Upregulated in M2 macrophages miR-122-5p XIAP M2 macrophages secrete SBF2-AS1-rich exosomes to promote tumor progression. [43]
LINC00662 Macrophages HCC Upregulated in tumor cells miR-15a, miR-16, miR-107 WNT3A, Wnt/β-catenin signaling Increasing tumor-derived WNT3A and activating Wnt/β-catenin signaling in macrophages via paracrine manner, and promoting M2 macrophages polarization Overall survival, differentiation, tumor size, microvascular invasion [45]
MALAT1 Macrophages HCC Upregulated in tumor cells miR-140 VEGF-A Regulating macrophage polarization [46]
RPPH1 Macrophages Colorectal cancer Upregulated in tumor cells TUBB3 Inhibiting TUBB3 ubiquitination and enhancing exosomes-mediated macrophages M2 polarization and influences the tumor microenvironment Overall survival, TNM stages [47]
BCRT1 Macrophages Breast cancer Upregulated in tumor cells and M2 [45]macrophages miR-1303 PTBP3 Promoting M2 polarization of macrophages, mediated by exosomes, and accelerating cancer progression Overall survival [48]
TUC339 Macrophages HCC Upregulated in HCC-derived exosomes Regulating macrophage activation and polarization [49]
CASC2c Macrophages Glioblastoma Downregulated in tumor cells miR-338-3p FX Inhibiting macrophage migration and polarization to the M2 subtype by FX [50]
CamK-A Macrophages Breast cancer Upregulated in tumor cells PNCK, IκBα, NF-κB, VEGF, IL-8, and GLUT3 Promoting infiltrated macrophage recruiting, angiogenesis, tumor microenvironment remodeling, and cancer development,  Overall survival, recurrence-free survival  [51]
Lnc-C/EBPβ MDSCs Upregulated in MDSCs C/EBPβ isoform LIP  Controlling immunosuppressive function and differentiation of MDSCs by a set of target transcripts [52]
Lnc-C/EBPβ MDSCs Upregulated IL4il, C/EBPβ isoform LIP, WDR5 Promoting PMN-MDSCs but impede differentiation of M-MDSCs [53]
RNCR3 MDSCs Upregulated in MDSCs miR-185-5p Chop Regulating MDSC differentiation and suppressive function to influence tumor growth by RNCR3/miR-185-5p/Chop axis [54]
Lnc-chop MDSCs Upregulated in MDSCs CHOP, C/EBPβ isoform LIP Interacting with CHOP and the C/EBPβ isoform LIP to regulate immunosuppressive function of MDSCs [55]
Olfr29-ps1 MDSCs Upregulated miR-214-3p MyD88  Regulating the differentiation and function of M-MDSCs by a m6A-modified Olfr29-ps1/miR-214-3p/MyD88 regulatory network [56]
Pvt1 MDSCs Upregulated C-myc Regulating the immunosuppression activity of PMN-MDSCs by c-myc [57]
AK036396 MDSCs Upregulated Ficolin B Inhibiting maturation and accelerating immunosuppression of PMN-MDSCs by Enhancing the Stability of Ficolin B [58]
MALAT1 MDSCs Lung Cancer Downregulated  Negatively regulating the generation of MDSCs [59]
RUNXOR MDSCs Lung cancer Upregulated RUNX1  Mediating MDSCs associated immunosuppression by targeting RUNX1 Smoking history, TNM stage, histological tumor type and lymph node metastasis [60]
HOTAIRM1 MDSCs Lung Cancer Downregulated  HOXA1  Regulating MDSCs associated immunosuppression by targeting HOXA1 Smoking history, TNM stage, histological tumor type and lymph node metastasis [61]
HOTAIR MDSCs HCC Upregulated CCL2 Promoting proliferation of macrophages and MDSCs  [62]
Gm43181 Neutrophils Upregulated in neutrophils CXCR2 Provoking inflammation by regulating the recruitment and activation of neutrophils into the specific tissues [63]
MALAT1 Neutrophils Upregulated p300, IL-8 Ameliorating the inflammatory injury by inhibiting chemotaxis of neutrophils through p300-mediated downregulation of IL-8  [64]
XIST Neutrophils Upregulated miR-21 IL-12A Increasing IL-12A by binding to miR-21, thereby inducing neutrophil extracellular trap formation  [65]
TCL6 Neutrophils Breast cancer Downregulated in tumor cells Overall survival [11]
HOTTIP Neutrophils Ovarian cancer Upregulated in tumor cells c-jun, IL-6, PD-L1 Enhancing IL-6 expression to potentiate immune escape of tumor cells by upregulating the expression of PD-L1 in neutrophils Overall survival [66]
Lnc-DC DCs Upregulated in DCs  STAT3, TLR9, TIMP, MMP Regulating the differentiation and capacity of DCs by activating the transcription factor STAT3 [67,68,69,70]
NEAT1 DCs Upregulated in DCs miR-3076-3p NLRP3 Inducing tolerogenic phenotype in DCs by inhibiting activation of NLRP3 inflammasome [71]
HOTAIRM1  DCs Downregulated in DCs miR-3960 HOXA1 Regulating DC differentiation by competitively binding to endogenous miR-3960 [72]
Lnc-Dpf3 DCs Upregulated in DCs HIF-1α CCR7-inducible lnc-Dpf3 restrains DC migration by inhibiting HIF-1α-mediated glycolysis [73]
MALAT-1 DCs Colon cancer Upregulated in DCs Snail Blocking MALAT-1 significantly decreases the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the Snail [74]
SNHG16 B cells DLBCL Upregulated in tumor cells miR-497-5p PIM1 Promoting proliferation and inhibits apoptosis of lymphoma cells by targeting miR-497-5p/PIM1 axis [75]
TUG1 B cells DLBCL Upregulated in tumor cells MET  Regulating tumor growth by ubiquitination of MET [76]
SNHG14 B cells DLBCL Upregulated in tumor cells miR-5590-3p ZEB1 SNHG14/miR-5590-3p/ZEB1 positive feedback loop promotes lymphoma progression and immune evasion by PD-1/PD-L1 checkpoint [77]
MALAT1 B cells DLBCL Upregulated in tumor cells miR-195 PD-L1 Promoting tumorigenesis and immune escape of lymphoma by sponging miR-195 [78]
MINCR B cells BL Upregulated in tumor cells AURKA, AURKB, and CDT1 Controlling cell cycle by participating in MYC transcriptional network [79]
NEAT1 B cells DLBCL Upregulated in tumor cells miR-34b-5p GLI1 Promoting B cell proliferation and lymphomagenesis by the miR-34b-5p-GLI1 pathway. [80]
FIRRE B cells DLBCL Upregulated in tumor cells Wnt/β-catenin pathway Promoting the development of lymphoma by Wnt/β-catenin signaling pathway Overall survival [81]
PANDA B cells DLBCL Downregulated in tumor cells MAPK/ERK pathway Inhibiting the growth of lymphoma by inactivation of MAPK/ERK signaling pathway Overall survival, recurrence-free survival, B symptoms, Ann arbor stages, CHOP-like treatment, Rituximab and IPI [82]
OR3A4 B cells DLBCL Upregulated in tumor cells  Wnt/β-catenin signaling Promoting cell proliferation through activating Wnt/β-catenin signaling pathway Overall survival [83]
SMAD5-AS1 B cells DLBCL Downregulated in tumor cells miR-135b-5p APC, Wnt/β-catenin pathway Inhibiting proliferation of lymphoma through Wnt/β-catenin pathway via targeting miR-135b-5p to elevate expression of APC [84]
HULC B cells DLBCL Upregulated in tumor cells Bcl-2, cyclin D1 Regulating cell proliferation and inducing apoptosis by Bcl-2 and cyclin D1 Overall survival, progression–free survival, Ann Arbor stages, B symptoms, CHOP-like treatment, Rituximab and IPI [85]
HOTAIR B cells DLBCL Upregulated in tumor cells PI3K/AKT/NF-κB pathway Promoting cell proliferation by PI3K/AKT/NF-κB pathway Overall survival, tumor size, clinical stage, B symptoms and IPI [86]
LUNAR1 B cells DLBCL Upregulated in tumor cells E2F1, cyclin D1 and p21 Regulating cell proliferation by E2F1, cyclin D1 and p21 Overall survival, progression-free survival, stage, rituximab and IPI [87]
PEG10 B cells DLBCL Upregulated in tumor cells Overall survival, B symptoms, CHOP-like treatment, Rituximab and IPI [88]
MALAT-1 B cells DLBCL Upregulated in tumor cells LC3-II/LC3-I, p62, ATG5  Regulating autophagy-related signaling pathway on chemotherapy resistance [89]
FAS-AS1 B cells Non-Hodgkin's lymphomas Upregulated in tumor cells RBM5 Regulating of the sFas expression by interacting with RBM5 to influence cell apoptosis [90]
FENDRR Tregs HCC Downregulated in Tregs miR-423-5p GADD45B  Inhibiting the Treg-mediated immune escape of tumor cells through upregulating GADD45B by sponging miR-423-5p [91]
SNHG1 Tregs Breast cancer Upregulated in Tregs miR-448 IDO Accelerating the differentiation of Treg cells and promoting the immune escape of cancer by regulating miR-448/IDO axis [92]
POU3F3 Tregs Gastric cancer Upregulated in Tregs TGF-β/SMAD2/3 pathway Promote the distribution of Tregs in peripheral blood T cell, increasing cell proliferation by recruiting TGF-β as well as activating TGF-β signal pathway Tumor size [93]
lnc-EGFR Tregs HCC Upregulated in Tregs EGFR, AP-1/NF-AT1 axis Stimulating Treg differentiation, suppresses CTL activity and promoting HCC growth in an EGFR-dependent manner.  Tumor size [94]
RP11-323N12.5 Tregs Gastric cancer Upregulated in tumor cells YAP1, TAZ, TEAD, Hippo signaling Promoting Treg cell differentiation by enhancing YAP1 transcription in T cells Disease-free survival, stage [95]
SNHG16 Tregs Breast cancer Upregulated in tumor cells miR-16-5p SMAD5  Breast cancer-derived exosomes transmit SNHG16 to induce CD73+γδ1 Treg cells by activation of the TGF-β1/SMAD5 pathway [96]
Lnc-sox5 CTLs Colorectal cancer Upregulated in tumor cells IDO1 Regulating the infiltration and cytotoxicity of CD3+CD8+T cells by IDO1, and unbalancing the TME Metastasis [97]
NEAT1 CTLs Lung cancer Upregulated in tumor cells DNMT1, P53, cGAS/STING Interacting with DNMT1 to regulate malignant phenotype of cancer cell and cytotoxic T cell infiltration by epigenetic inhibition of p53, cGAS, and STING  Tumor stage, lymph node metastasis. [98]
NEAT1 CTLs HCC Upregulated in CTLs miR-155 Tim-3 Regulating the antitumor activity of CD8+ T cells against HCC by miR-155/Tim-3 axis [99]
 Lnc-Tim3 CTLs HCC Upregulated in CTLs Tim-3, Bat3, Lck/ NFAT1/AP-1 pathway Exacerbating CD8+ T cell exhaustion by binding to Tim-3 and inducing nuclear translocation of Bat3 [100]
LINC00473 CTLs Pancreatic cancer Upregulated in tumor cells miR-195-5p PD-L1 Inhibiting activation of CD8+ T cells by sponging miR‐195‐5p to elevate the expression of PD‐L1 [101]
SNHG14 CTLs DLBCL Upregulated in tumor cells miR-5590-3p ZEB1, PD-1 Promoting apoptosis of CD8+ T cells by PD-1/PD-L1 immune checkpoint, and eventually leading to the immune evasion [77]
MALAT1 CTLs DLBCL Upregulated in tumor cells miR-195 PD-L1 Promoting apoptosis of CD8+ T cells and immune escape of lymphoma [78]
GM16343 CTLs Upregulated in CTLs IFN-γ Promoting IL-36β to regulate the TME by CD8+ T cells Overall survival [102]
NKILA CTLs breast and lung cancer  Upregulated in CTLs NF-κB Regulating T cell sensitivity to AICD by inhibiting NF-κB activity Overall survival [103]
INCR1 CTLs Upregulated in CTLs PD-L1, JAK2, STAT1, and IDO1, HNRNPH1 Regulating tumor IFNγ signaling and CTL-mediated killing [104]
Lnc-CD56 NK cells Upregulated in NK cells CD56 Serving as a positive regulator of CD56 in primary human NK cells and differentiated NK cells from human CD34+ hematopoietic progenitor cells.  [105]
IFNG-AS1 NK cells Upregulated in NK cells IFNG Triggering of the natural cytotoxicity receptors induces lncRNA IFNG-AS1 expression, and IFNG-AS1 increases IFN-γ secretion [106]
GAS5 NK cells Gastric cancer Downregulated in NK cells miR-18a Promoting NK cell cytotoxicity against gastric cancer by regulating miR-18a [107]
GAS5 NK cells HCC Downregulated in NK cells miR-544 RUNX3 Enhancing the killing effect of NK cell on liver cancer by regulating miR-544/RUNX3 [108]
linc-EPHA6-1 NK cells Lung cancer miR-4485-5p NKp46  IFNβ-induced exosomal linc-EPHA6-1 promotes cytotoxicity of NK cells by miR-4485-5p to increase NKp46 expression [109]
  1. Abbreviations:AICD Activation-induced cell death, BL Burkitt lymphoma, CTLs Cytotoxic T lymphocytes, DCs Dendritic cells, DLBCL Diffuse large B cell lymphoma, HCC Hepatocellular carcinoma, HGSOC High-grade serous ovarian cancer, IPI International prognostic index scores, NK Natural killer, TNBC Triple-negative breast cancer, Tregs Regulatory T cells