Table 2.
miRNAs in CAF
| miRNAs (expression) | Effects on cancer cells and mechanism of action | Potential targeting therapy | Ref. |
|---|---|---|---|
| Lung cancer | |||
| miR-1 (↓) | Proliferation, chemoresistance by NF-κB and Bcl-xl pathwaya | Pathway | 399 |
| miR-101 (↓) | Growth, metastasis by CXCL12 and PI3K-Akt pathwaya | Restoring miR-101 | 400 |
| miR-210 (↑) | Migration, proliferation, invasion, EMT by PI3K/AKT pathwaya | Exosomal mRr-210 | 401 |
| miR-1/206 (↓) | Angiogenesis, TAMs accumulation, growth, metastasis by FOXO3a/VEGF/CCL2 signaling | Delivery of pre-miR-1/206 and anti-miR-31 | 402 |
| miR-31 (↑) | |||
| Breast cancer | |||
| miR-1-3p (↓) | Progression, metastasis by GLIS1 gene | MiR-1-3p EVs | 403 |
| miR‐22 (↑) | Chemoresistance by PI3K‐AKT pathway | Nanoparticles | 404 |
| miR-26b (↓) | Migration, invasion via TNKS1BP1/CPSF7/COL12A1a | MiR-26b | 405 |
| miR-29b (↓) | Growth, chemoresistance, migration by p38-STAT1 pathway | Suppressor miR-29b | 354 |
| miR-92 (↑) | PD-L1; migration, proliferation by LATS2 of Hippo pathway | MiR-92 inhibitor | 406 |
| miR-200b/c (↓) | Growth, active mobility, invasion by NF-κB pathway | Pathway | 407 |
| miR-200s (↓) | Invasion, metastasis via transcription factors Fli-1 and TCF12 | MiR-200s | 408 |
| miR-205 (↓) | Angiogenesis by targeting YAP1 through STAT3 pathway | Pathway | 409 |
| miR-221 (↑) | Growth, migratory by A20/c-Rel/CTGF signalinga | LNA-i-miR-221 | 272 |
| miR-320 (↓) | Proliferation, invasion by PI3K/AKT pathway | MiR-320 agents | 410 |
| miR-181d-5p (↑) | EMT via transcription factor CDX2 and HOXA5a | Exosomal miR-181d-5p | 411 |
| miR-3613-3p (↑) | Proliferation, metastasis by SOCS2 gene expressiona | Exosomal miR-3613-3p | 412 |
| miR-4516 (↓) | Proliferation by targeting FOSL1 genea | MiR-4516 agents | 413 |
| miR-16/148a (↑) | Migration, metastasis by FAK pathway | Pathway | 414 |
| miR-141 (↓) | MiR-200b/c/miR-221/DNMT3B feedback loop influencing TGF-β1 expression, and TGF-β1/DNMT3B/miR-141 axis enhancing TCF12 in CAF to promote cancer cell proliferationa | Regulatory loop/axis | 415 |
| miR-221 (↑) | |||
| miR-200b/c (↓) | |||
| Prostate cancer | |||
| miR-15/16 (↓) | Proliferation and capability of CAF by FGF2 and FGFR1 | Restoring miR-15/16 | 416 |
| miR-146a-5p (↓) | Metastasis, invasion by EGFR/ERK pathway | Exosomal miR-146a-5p | 417 |
| miR-409 (↑) | Tumorigenesis, EMT, and stemness by tumor suppressor genes | MiR-409 | 418 |
| miR-423-5p (↑) | Chemoresistance by the TGF-β signaling pathway | MiR-423-5p inhibitor | 419 |
| Colorectal cancer | |||
| miR-21 (↑) | Motility and invasion by MMP inhibitor RECKa | MiR-21 | 420 |
| miR-31 (↑) | Radiosensitivity via genes Beclin-1, ATG, DRAM, and LC3a | MiR-31 | 421 |
| miR-92a-3p (↑) | Stemness, EMT, metastasis, and chemoresistance by activating Wnt/β-catenin pathway and inhibiting mitochondrial apoptosis | Inhibiting exosomal miR-92a-3p | 422 |
| miR-93-5p (↑) | Radioresistance by TGF-β signaling pathway | Exosomal miR-93-5p | 367 |
|
miR-17/192 (↓) miR-200c (↓) |
Invasion by regulating ECM target genes on the protein levela | Restoring miR-17/192, and/or miR-200c | 423 |
| Gastric cancer | |||
| miR-34 (↓) | Proliferation and invasion by targeting 16 genes | Exosomal miR-34 | 424 |
| miR-106b (↑) | Migration and invasion by PTEN-mediated signaling pathwaya | MiR-106b | 425 |
| miR-139 (↓) | Growth and metastasis by downregulating MMP11 | Exosomal miR-139 | 308 |
| miR-149 (↓) | EMT and stem-like properties by COX-2/PGE2 signaling | MiR-149 | 426 |
| miR-214 (↓) | Migration and invasion by EMT and targeting FGF9a | MiR-214/FGF9 | 427 |
| miR-522 (↑) | Suppressing ferroptosis by targeting ALOX15 and blocking lipid-ROS accumulation, chemotoxicity promoting miR-522 secretion by activating USP7/hnRNPA1 pathway | Blocking miR-522 packaging into exosomes | 9 |
| Hepatocellular carcinoma | |||
| miR-29b (↓) | Invasion, migration, and apoptosis by DNMT3ba | MiR-29b mimic | 428 |
| miR-101 (↓) | Vascular mimicry formation by SDF-1 signaling | Signaling networks | 115 |
| miR-320a (↓) | Proliferation, migration, and metastasis by MAPK pathway | Transfer of miR-320a | 429 |
| miR-1247-3p (↑) |
Stemness, EMT, chemoresistance, and tumorigenicity by IL-6/8; lung metastasis by β1-integrin-NF-κB pathway |
Tumor–stromal crosstalk | 430 |
| Cholangiocarcinoma | |||
| miR-15a (↓) | Migration by regulating PAI-2 expressiona | MiR-15a/PAI-2 axis | 431 |
| Cervical and squamous cell carcinoma | |||
| miR-10a-5p (↑) | Angiogenesis and tumorigenicity by Hedgehog pathway | MiR-10a-5p evs | 432 |
| Pancreatic cancer | |||
| miR-21(↑) | Desmoplasia, drug resistance, and CAF activation by PDCD4 gene | MiR-21 | 433 |
| miR-106b (↑) | Chemoresistance by directly targeting TP53INP1 genea | Exosomal miR-106b | 309 |
| miR-146a (↑) | Proliferation and survival by gemcitabine-induced Snail pathway | Exosomal inhibitors | 70 |
| Head and neck cancer | |||
| miR-7 (↑) | Proliferation and migration via RASSF2 and decreasing PAR-4a | Inactivation of the RASSF2-PAR-4 axis | 434 |
| miR-34a-5p (↓) | Proliferation and metastasis by AKT/GSK3β/β-catenin pathway | MiR-34a-5p/AXL axis | 136 |
| miR-196a (↑) | Proliferation and resistance by regulating CDKN1B and ING5a | Exosomal miR-196a | 435 |
| miR-3188 (↓) | Proliferation and apoptosis by targeting BCL-2 | Exosomal miR-3188 | 436 |
| Melanoma | |||
| miR-155 (↑) | Angiogenesis by SOCS1/JAK2/STAT3 signaling pathway | Exosomal miR-155 | 437 |
| Osteosarcoma | |||
| miR-1228 (↑) | Migration and invasion by endogenous SCAI mRNA and proteina | Exosomal miR-1228 | 438 |
| Ovarian cancer | |||
| miR-21 (↑) | Motility, invasion, lowering chemosensitivity and apoptosis by binding to APAF1 coding sequence | Inhibiting miR-21 | 439 |
| miR-98-5p (↑) | Cisplatin resistance by downregulating CDKN1A | Exosomal miR-98-5p | 440 |
| miR-31/214 (↓) | Recruitment and growth by regulating CCL5 | MiRNAs | 441 |
| miR-155 (↑) | |||
| Endometrial cancer | |||
| miR-31 (↓) |
Motility and invasion by targeting partially the SATB2 homeobox gene |
MiR-31/SATB2 signal | 442 |
| miR-148a (↓) | Invasion by decreasing WNT10B in WNT/β-catenin pathwaya | Restoring miR-148a | 443 |
| miR-148b (↓) | EMT by relieving the suppression of gene DNMT1 | Transfer of miR-148b | 444 |
ALOX15 arachidonate lipoxygenase 15, AKT protein kinase B, APAF1 apoptotic protease-activating factor-1, Bcl-xL B cell lymphoma-extra large, CAF cancer-associated fibroblasts, CCL C–C chemokine ligand, CDKN cyclin-dependent kinase inhibitor, CDX2 caudal-related homeobox 2, COX-2 cyclooxygenase-2, CTGF connective tissue growth factor, CXCL C–X–C chemokine ligand, DNMT DNA methyltransferase, EGFR epidermal growth factor receptor, ECM extracellular matrix, EMT epithelial–mesenchymal transition, ERK extracellular signal-related kinase, EV extracellular vesicles, FAK focal adhesion kinase, FGF fibroblast growth factors, Fli-1 friend leukemia integration 1, FOXO3a Forkhead box O3, GLIS1 Gli-similar 1, GSK glycogen synthase kinase, hnRNPA1 heterogeneous nuclear ribonucleoprotein A1, HOXA5 homeobox A5, IL interleukin, ING5 inhibitor of growth 5, JAK Janus kinase, MAPK mitogen-activated protein kinases, MMP matrix metalloproteinases, NF-κB nuclear factor kappa-B, PAI-2 plasminogen activator inhibitor 2, PGE2 prostaglandin E2, PTEN phosphate and tensin homolog, PI3K phosphatidylinositol-3-kinase, ROS reactive oxygen species, SCAI suppressor of cancer cell invasion, SDF-1 stromal cell-derived factor-1, SOCS suppressor of cytokine signaling, STAT signal transducer and activator of transcription, TAMs tumor-associated macrophages, TCF12 transcription factor 12, TGF transforming growth factor, USP7 ubiquitin-specific protease 7, VEGF vascular endothelial-derived growth factor
aWithout xenograft models