Table 1.
Landscape of non-coding RNAs transmitted by small extracellular vesicles in pancreatic cancer, induced molecular pathways and effect on recipient cells
| ncRNA | Transmission by small extracellular vesicles | Target | Downstream signaling/molecular mechanism | Effect in recipient cells | Ref | |
|---|---|---|---|---|---|---|
| from… | to… | |||||
| microRNAs | ||||||
| 21-5p | TAM | PDAC | KLF3 | Stemness, invasion, migration | [83] | |
| PSCs | PDAC | Induction of Ras/ERK/Akt | Proliferation, migration | [106] | ||
| 27a | PDAC | Endothelial cells | BTG2 | Angiogenesis, tumor growth | [114] | |
| 106b | PSCs | PDAC | TP53INP1 | GEM resistance | [99] | |
| 125b-5p | Highly malignant PDAC | Less malignant PDAC | STARD13 | Induction of MEK2/ERK2 | Invasion, migration, EMT | [48] |
| 143 | hMSCs | PDAC | lncRNA-RP11-363N22.3 | Promotes apoptosis, inhibits proliferation, invasion, migration | [102] | |
| 145 | Primary tumor stroma | PDAC | Apoptosis | [101] | ||
| 146a | GEM-treated CAFs | PDAC | Induction of Snail | GEM resistance | [100] | |
| 155 | Pancreatic fibroblasts | CAFs | TP53INP1 | Conversion of PSCs into CAFs | [98] | |
| TAM | Endothelial cells | E2F2 | Angiogenesis, tumor growth | [113] | ||
| GEM-resistant PDAC | PDAC | TP53INP1 | GEM resistance | [127] | ||
| GEM-treated PDAC | PDAC | DCK | GEM resistance | [126] | ||
| 203 | PDAC | Dendritic cells | TLR4 | Inhibition of TNF-α/IL-12 expression | Immunosuppression | [72] |
| 210 | GEM-treated CSCs | regular PDAC | Induction of mTOR | Stemness, GEM resistance | [131] | |
| 212-3p | PDAC | Dendritic cells | RFXAP | Inhibition of MHC II expression | Immunosuppression | [72] |
| 221-5p | TAM | Endothelial cells | E2F2 | Angiogenesis, tumor growth | [113] | |
| 222 | Highly malignant PDAC | Less malignant PDAC | PPP2R2A | Induction of AKT, inhibition of p27 import to the nucleus | Proliferation, invasion, migration | [49] |
| 301a-3p | Hypoxic PDAC | Macrophages | PTEN | Induction of PI3K/AKT/mTOR | M1-to-M2 polarization of macrophages, immunosuppression | [84] |
| 365 | TAM | PDAC | BTG2 | Induction of FAK/AKT | Proliferation, invasion, migration | [78] |
| Increase of intracellular NTPs and CDA | GEM resistance | [77] | ||||
| 494 | PDAC | LN stroma cells, lung fibroblasts | CDH17 | Promotes pre-metastatic niche | [58] | |
| PBMCs | Increase of intracellular calcium fluxes | Expansion of MDSCs and immunosuppression | [74] | |||
| 501-3p | TAM | PDAC | Induction of TGFBR3 | Anti-apoptosis, proliferation, stemness, invasion, migration | [82] | |
| Endothelial cells | Angiogenesis | |||||
| 542-3p | PDAC | LN stroma cells, lung fibroblasts | CDH17 | Promotes pre-metastatic niche | [58] | |
| 616-3p | hypoxic PSCs | PDAC | PTEN | Induction of AKT | Proliferation, invasion, migration | [107] |
| 1260a | PDAC | PBMC | Increase of intracellular calcium fluxes | Expansion of MDSCs and immunosuppression | [74] | |
| 1290 | PDAC | PSCs | Induction of ERK/Akt | Conversion of PSCs into profibrotic CAFs | [97] | |
| 3607-3p | natural killer cells | PDAC | IL-26 | Inhibits proliferation, invasion, migration | [76] | |
| 4465 | hypoxic PSCs | PDAC | PTEN | Induction of AKT | Proliferation, invasion, migration | [107] |
| 5703 | PSCs | PDAC | CMTM4 | Induction of PAK4/PI3K/Akt | Proliferation | [108] |
| Long non-coding RNAs | ||||||
| CCAT1 | PDAC | Endothelial cells | miR-138-5p | Induction of HMGA1 | Angiogenesis, tumor growth | [115] |
| HULC | PDAC | PDAC | EMT, invasion, migration | [56] | ||
| SBF2-AS1 | TAM | PDAC | miR-122-5p | Induction of XIAP | Proliferation, invasion, migration | [79] |
| Sox2ot | Highly malignant PDAC | Less malignant PDAC | miR-200 family | Induction of Sox2 | Stemness, EMT, metastasis | [53] |
| UCA1 | Hypoxic PDAC | Endothelial cells | miR-96-5p | Induction of AMOTL2/ERK1/2 | Angiogenesis, tumor growth | [116] |
| Circular RNAs | ||||||
| 0000069 | PDAC | Benign pancreas | Induction of STIL | Cell cycle progression, proliferation, migration | [59] | |
| 0030167 | BM-MSCs | PDAC | miR-338-5p | Induction of Wif1, inhibition of Wnt8/β-catenin | Inhibits proliferation, invasion, migration, stemness | [103] |
| IARS | PDAC | Endothelial cells | miR-122 | Endothelial permeability, metastasis | [57] | |
| PDE8A | Highly malignant PDAC | Less malignant PDAC | miR-338 | Induction of MACC1/MET/ERK/AKT | Proliferation, invasion, metastasis | [47] |
| ZNF91 | Hypoxic PDAC | Normoxic PDAC | miR-23b-3p | Induction of SIRT1 and glycolysis | GEM resistance | [133] |
BM-MSC, bone marrow mesenchymal stem cell; CAF, cancer-associated fibroblast; CDA, cytidine deaminase; CSC, cancer stem cell; DCK, deoxycytidine kinase; EMT, epithelial-to-mesenchymal transition; GEM, gemcitabine; hMSC, human mesenchymal stem cell; LN, lymph node; NTP, nucleotide triphosphate; PBMC, peripheral blood mononuclear cell; PSC, pancreatic stellate cell; Ref., reference; TAM, M2-polarized tumor-associated macrophage