Table 1.
The biological functions of EV ncRNAs in LC
| ncRNAs | Dysregulation | Target | Experiment type (in vitro/in vivo) | Biological functions | Reference |
|---|---|---|---|---|---|
| miR-9 | – | SOCS5 | in vitro (NSCLC cells→ endothelial cells) | promote endothelial cell migration and angiogenesis | Zhuang et al.121 |
| miR-21 | upregulated | PDCD4 | in vitro (LAC cells→ osteoclasts) | promote tumor osteolytic metastasis | Xu et al.122 |
| miR-21/miR-29a | upregulated | TLR8 | in vitro (LLCs→ macrophages); in vivo (mouse LC model, intravenously injected with LLC-secreted EVs) | trigger pre-metastatic inflammatory response | Fabbri et al.123 |
| miR-21a | upregulated | PDCD4 | in vitro (LLCs→ MDSCs); in vivo (mouse LC model, intravenously injected with LLC-secreted EVs) | promote MDSCs expansion and accumulation, promote cancer cell growth | Zhang et al.124 |
| miR-23a | upregulated | ZO-1 | in vitro (hypoxic LC cells → endothelial cells); in vivo (human, serum EVs) | promote angiogenesis, increase migration | Hsu et al.125 |
| miR-31-5p | upregulated | SATB2 | in vitro (hypoxic LC cells → endothelial cells); in vivo (human, plasma EVs) | promote migration, invasion, and metastasis | Yu et al.126 |
| miR-96 | upregulated | LMO7 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote cell proliferation, migration, and DDP resistance | Wu et al.127 |
| miR-100-5p | Downregulated | – | in vitro (A549/DDP cells → A549 cells); in vivo (mouse LC model, intratumorally injected with A549/DDP cell-secreted EVs) | alter other LC cells' sensitivity to DDP | Qin et al.128 |
| miR-103a | upregulated | PTEN | in vitro (hypoxic LC cells → M2 macrophages) | increase M2 macrophage polarization | Hsu et al.129 |
| miR-130a | – | PUM2 | in vitro (CAFs → DDP-sensitive NSCLC cells) | promote survival of DDP-sensitive NSCLC cells | Zhang et al.130 |
| miR-142-3p | upregulated | TGFbetaR1 | in vitro (LAC cells → endothelial and fibroblast cells) | promote angiogenesis and cancer-associated fibroblast phenotype | Lawson et al.131 |
| miR-143-3p | upregulated | ITM2B | in vitro (MDSCs →LC cells); in vivo (mouse LC model, intratumorally injected with MDSC-secreted EVs) | promote proliferation | Zhou et al.132 |
| miR-144 | Downregulated | CCNE1/2 | in vitro (BMSCs →NSCLC cells); in vivo (mouse LC model, intravenously injected with BMSC-secreted EVs) | inhibit proliferation | Liang et al.133 |
| miR-192 | Downregulated | – | in vitro (NSCLC cells → osteoclasts); in vivo (mouse LC model, intravenously injected with NSCLC cell-secreted EVs) | inhibit angiogenesis and osteoclastogenesis | Valencia et al.134 |
| miR-193a | – | LRRC1 | in vitro (BMSCs → NSCLC cells); in vivo (mouse LC model, intravenously injected with BMSC-secreted EVs) | promote proliferation, migration, invasion, and DDP-resistant cell apoptosis | Wu et al.135 |
| miR-193a-3p, miR-210-3p, and miR-5100 | upregulated | – | in vitro (hypoxic BMSCs → Epithelial cancer cells); in vivo (human, plasma EVs; mouse LC model, intravenously injected with hypoxic BMSC-secreted EVs) | promote invasion and EMT | Zhang et al.136 |
| miR-210 | upregulated | TET2 | in vitro (LC cells →fibroblasts); in vivo (human, plasma EVs; mouse angiogenesis model, fibroblasts mixed with LC cell-secreted EVs) | promote fibroblasts transfer into CAFs and angiogenesis | Fan et al.137 |
| miR-222-3p | – | SOCS3 | in vitro (A549/GR cells → A549 cells); in vivo (human, plasma EVs; mouse LC model, injected with A549/GR cell-secreted EVs) | promote proliferation, migration, invasion, and gemcitabine resistance | Wei et al.138 |
| miR-214 | upregulated | – | in vitro (PC-9/GR cells → PC-9 cells); in vivo (mouse LC model, hypodermic injected with PC-9/GR cell-secreted EVs) | promote gefitinib resistance | Zhang et al.139 |
| miR-302b | upregulated | TGFbetaRII | in vitro (lowly metastatic LC cells → highly metastatic LAC cells) | suppress LC cell proliferation and migration | Li et al.140 |
| miR-369 | upregulated | NF1 | in vitro (CAFs → LAC cells); in vivo (mouse LC model, hypodermic injected with CAF-secreted EVs) | promote proliferation, migration, and invasion | Guo et al.141 |
| miR-425-3p | upregulated | AKT | in vitro (DDP-resistant NSCLC cells → DDP-sensitive NSCLC cells); in vivo (human, serum EVs) | facilitated autophagic activation and chemoresistance | Ma et al.142 |
| miR-486-5p | Downregulated | NEK2 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | induce cell-cycle arrest, inhibit cell proliferation, and metastasis | Hu et al.143 |
| miR-499a-5p | upregulated | mTOR | in vitro (highly metastatic LAC cells → LAC cells) | promote cell proliferation, migration, and EMT | He et al.144 |
| miR-564 and miR-658 | upregulated | – | in vitro (PC-9/gefitinib cells → PC-9 cells) | induce drug resistance in sensitive cells | Azuma et al.145 |
| miR-619-5p | upregulated | RCAN1.4 | in vitro (NSCLC cells → endothelial cells); in vivo (human, plasma EVs) | promote proliferation, metastasis, and angiogenesis | Kim et al.146 |
| miR-5787, miR-4532, and miR-4488 | upregulated | – | in vitro (mesenchymal cells → epithelial cells) | promote migration, invasion, and EMT | Tang et al.147 |
| circSATB2 | upregulated | miR-326 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote cell proliferation, migration, and invasion | Zhang et al.148 |
| circARHGAP10 | upregulated | miR-638 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote proliferation, migration, invasion, and glycolysis | Fang et al.149 |
| circUSP7 | upregulated | miR-934 | in vitro (NSCLC cells → CD8+ T cells); in vivo (human, plasma EVs) | inhibits CD8+ T cell function, promote resistance to immunotherapy | Chen et al.150 |
| lncHOTAIR | upregulated | miR-203 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote proliferation, migration, and invasion | Zhang et al.83 |
| lncMALAT-1 | upregulated | – | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote cell growth and migration, inhibit apoptosis | Zhang et al.151 |
| lncUFC1 | upregulated | EZH2 | in vitro (NSCLC cells → NSCLC cells); in vivo (human, serum EVs) | promote proliferation, migration, and invasion | Zang et al.152 |
| lncRNA-p21 | upregulated | – | in vitro (LC cells → HUVECs); in vivo (human, plasma EVs) | promote tube formation and enhance tumor cell adhesion to endothelial cells | Castellano et al.153 |
| lncGAS5 | Downregulated | miR-29-3p | in vitro (LC cells →HUVECs); in vivo (mouse LC model, serum EVs) | promote proliferation and tube formation, inhibit apoptosis | Cheng et al.154 |
| lncAGAP2-AS1 | upregulated | miR-296 | in vitro (M2 macrophage → NSCLC cells) | promote the radiotherapy immunity | Zhang et al.155 |
| lncPCAT-1 | upregulated | miR-182/miR-217 | in vivo (human, serum EVs) | promote pre-metastatic niche formation and tumor metastasis; induce G0/G1 cell-cycle arrest; promote chemoresistance and tumor growth | Domvri et al.156 |
| lncRNA MSTRG.292666.16 | upregulated | – | in vitro (osimertinib-resistant cells → osimertinib-sensitive cells); in vivo (human, plasma EVs) | associated with asimertinib resistance | Deng et al.86 |
| lncRNA RP11838N2.4 | upregulated | – | in vitro (erlotinib-resistant cells → erlotinib-sensitive cells); in vivo (human, serum EVs) | promote erlotinib resistance | Zhang et al.157 |
| lncRNA H19 | upregulated | – | in vitro (gefitinib-resistant NSCLC cells → gefitinib-sensitive NSCLC cells) | promote gefitinib resistance | Lei et al.158 |
NSCLC, non-small cell lung cancer; LAC, lung adenocarcinoma; LLC, Lewis LAC; LC, lung cancer; EV, extracellular vesicle; MDSC, myeloid-derived suppressor cell; DDP, cisplatin; CAF, cancer-associated fibroblast; BMSC, bone marrow mesenchymal stem cell; GR, gemcitabine resistance; EMT, epithelial-mesenchymal transition; HUVEC, human umbilical vein endothelial cell.