Table 2 The effect of exosomal miRNAs in the tumor microenvironment (TME)
miRNAs | The source of miRNAs | The effect of miRNAs & Mechanism of action |
|---|---|---|
miR-21 | Glioma | Induce angiogenesis by targeting VEGF/p-FLK/ VEGFR2 signaling pathway [113] |
miR-210-3p | HCC | Induce angiogenesis by targeting SMAD4 and STAT6 [117] |
miR-142-3p | NSCLC | Induce angiogenesis by inhibiting TGFβR1, PDGFR-β, and p SMAD2/3 [116] |
miR-141-3p | Ovarian Cancer | Induce angiogenesis by activating the JAK-STAT3 pathway [121] |
miR-23a | NPC | Induce angiogenesis by targeting TSGA10 and modulate the growth, migration, and tube formation of HUVECs [112] |
miR-100 | MSCs | Induce angiogenesis by targeting the mTOR/HIF-1α/VEGF signaling axis [118] |
miR-619-5p | NSCLC | Induce angiogenesis by inhibiting the expression of RCAN1.4 [115] |
miR-15a miR-181b miR-320c miR-874 | HLSC | Inhibit tumor angiogenesis by downregulation of the target genes including ITGB3, FGF1, EPHB4, and PLAU [126] |
miR-205 | Ovarian Cancer | Induce angiogenesis by targeting the PTEN/AKT pathway [120] |
miR-25-3p | Colorectal Cancer | Induce angiogenesis by targeting KLF2 and KLF4 through the VEGFR2/p-Erk/p-Akt pathway and ZO-1/Occludin/Claudin5 pathway respectively [124] |
miR-23a | Lung Cancer | Induce angiogenesis by inhibiting PHD1, PHD2, and ZO-1 and accumulating HIF-1α [125] |
miR-9 | Glioma | Induce angiogenesis by targeting the MYC/OCT4 pathway [114] |
miR-451a | HCC | Inhibit angiogenesis by targeting LPIN1 [127] |
miR-9 | NPC | Inhibit angiogenesis by regulating MDK and activating the PDK/Akt signaling pathway [128] |
miR-126a | MDSCs | Induce angiogenesis by activating inflammatory circuits and increasing IL-13 and IL-33 [119] |
miR-212-3p | Pancreatic Cancer | Suppress the immune system by interfering with DCs function by targeting MHC II TF RFXAP resulting in reduced expression of HLA-DR, -DP, and -DQ molecules [139] |
miR-203 | Pancreatic Cancer | Suppress the immune system by Influence on NKs activation by reducing TLR4, TNF-α, and IL-12 levels in DCs [140] |
miR-let-7i | Breast cancer | Suppress the immune system by changing the levels of IL-6, IL-17, IL-1b, TGFβ, SOCS1, KLRK1, IFNγ, and TLR4 [142] |
miR-150-5p miR-142-3p | Treg | Suppress the immune system by stimulating a cell-refractory phenotype of DCs, resulting in increased IL-10 and decreased IL-6 levels [141] |
miR-let-7d | Treg | Suppress the immune system by inhibiting Th1 cell proliferation and IFNγ secretion [65] |
miR-125b | NSCLC | Enhancing the immune system by macrophage repolarization to M1 phenotype [159] |
miR-125b-5p | Melanoma | Enhancing the immune system by targeting LIPA and increasing IL-1β, CCL1, CCL2, and CD80 marker’s level of M1 phenotype [5] |
miR-21 | Head and Neck Cancer | Suppress the immune system by macrophage polarization to M2 phenotype and increasing MRC1 level of M2 [137] |
miR-222-3p | EOC | Suppress the immune system by macrophage polarization to M2 phenotype by phosphorylation of STAT3 and downregulating SOCS3 [134] |
miR-21-3p miR-125b-5p miR-181d-5p miR940 | EOC | Suppress the immune system by TAMs polarization to M2 phenotype [135] |
miR-301a-3p | Pancreatic Cancer | Suppress the immune system by M2 phenotype polarization of macrophages by activation of the PTEN/PI3Kγ signaling pathway [160] |
miR-1246 | Colon Cancer | Suppress the immune system by M2 phenotype polarization of macrophages by increasing IL-10, TGFβ, and MMPs level [136] |
miR-155 | CLL | Suppress the immune system by reprogramming conventional monocytes into MDSCs by nuclear translocation of NFkB and phosphorylation of STAT1 [144] |
miR-10a | Glioblastoma | Suppress the immune system by abnormal differentiation of MDSCs by targeting RORA through the NFκB pathway [143] |
miR-21 | Glioblastoma | Suppress the immune system by abnormal function of MDSCs by targeting PTEN through the p-STAT3/p-p65/p-Akt pathway [143] |
miR-124 | Ovarian Cancer | Remodel ECM by differentiating NFs into CAFs by targeting SPHK1 and upregulation α-SMA and FAP [147] |
miR-27b-3p miR-214-3p | Myeloma | Remodel ECM by activation of fibroblast marker, α-SMA, and FAP, through targeting the FBXW7 and PTEN/AKT/GSK3 pathways [148] |
miR-27a | Gastric Cancer | Remodel ECM by differentiating NFs into CAFs by decreasing the level of CSRP2, and increasing the level of α-SMA [149] |
miR-10b | Colorectal Cancer | Remodel ECM by differentiating NFs into CAFs by inhibiting PIK3CA level and PI3K/Akt/mTOR pathway activity, increasing the level of TGF-β and α-SMA [150] |
miR-21 | HCC | Remodel ECM and enhance angiogenesis by reprogramming hepatic stellate cells (HSCs) into CAFs by targeting PTEN, activating PDK1/Akt signaling, and increasing VEGF, MMP2, MMP9, bFGF, and TGF-β [152] |
miR-9 | Breast Cancer | Remodel ECM by differentiating NFs into CAFs by affecting MMP1, EFEMP1, and COL1A1 [154] |
miR-105 | Breast Cancer | Remodel ECM by reprogramming stromal cells by activating MYC signal transduction in CAFs [155] |
miRNA-142- 3p | Lung Cancer Cells | Remodel ECM by differentiating NFs into CAFs [116] |
miR-155 | Melanoma | Remodel ECM and enhance angiogenesis by reprogramming NFs into CAFs by inhibiting SOCS1 and activating the JAK2/STAT3 signaling pathway and increasing levels of VEGFa, FGF2, and MMP9 in fibroblasts [151] |
miR‐1249‐5p miR‐6737‐5p miR‐6819‐5p | Colorectal Cancer | Remodel ECM by activating fibroblasts to CAFs by suppressing TP53 expression in fibroblasts [161] |
miR-1247 | HCC | Remodel ECM by activating β1-integrin–NF-κB signaling in fibroblasts to reprogramme into CAFs by targeting B4GALT3, leading to increasing in IL-6 and IL-8 levels [162] |