Table 3.
Major genes/pathways targeted by selected miRNAs in cancer
| miRNAs | Major genes/pathways targeted in cancer |
|---|---|
| miR-7 | Targets XRCC2 expression and EGFR signaling pathway.95,167 |
| miR-9 | Modulates the PI3K/AKT, JAK/STAT, Notch1, Wnt/β-catenin, Ras, and ERK signaling pathways.98 |
| miR-15a | Targets the oncogenes BCL2, MCL1, CCND1, and Wnt3A.99 |
| miR-17-92 cluster | Targets tumor-suppressive (PTEN, RB2, and TGF-β) and oncogenic (c-myc, Notch, and Sonic Hedgehog) signaling pathways.102,103 |
| miR-21 | Modulates PTEN, PDCD4, RECK, MAPK/ERK, PI3K/AKT, STAT3, and BCL2 gene expression.106 |
| miR-24 | Increases the oncogenes (c-myc, BCL2, HIF1) gene expression and reduces the tumor-suppressor (p21 and p53) protein expression.108 |
| miR-25 | Regulates E2F1 expression.168 |
| miR-26 | Targets caspase-3, caspase-9, and poly (ADP-ribose) polymerase.111 |
| miR-27a | Increases PI3K/AKT/GSK3β, Wnt/β-catenin, Ras/MEK/ERK, and c-myc signaling pathways, while inhibiting TGF-β pathway.112 |
| miR-34 | Activates p53; inhibits vimentin and fibronectin expression; promotes E-cadherin expression; controls Wnt, TGF-β/Smad, and Notch signaling pathways.115, 116, 117 |
| miR-96 | Targets the structural proteins (involved in cell migration and adhesion) and the FOXO transcription factors.119 |
| miR-125b | Suppresses the expression of BCL-2 family genes.169 |
| miR-126 | Reduces the PI3K, K-Ras, VEGF signaling pathways.123 |
| miR-132 | Modulates the PI3K, TGF-β, and Hippo signaling pathways; reduces the expression of oncogenes Ras, AKT, and mTOR.125 |
| miR-135 | Targets AKT and Wnt signaling pathways, and APC, FOXO1, FOXN1, RECK, some matrix metalloproteinases gene expression.126 |
| miR-144 | Modulates the Src/AKT/ERK, Notch, JAK2/STAT3, EGFR, and PTEN/PI3K/AKT signaling pathways.127 |
| miR-153 | Reduces PTEN expression.130 |
| miR-181 | Regulates the MAPK, ERK, Wnt, TGF-β, EGFR/Ras, PI3K/AKT, p53 signaling pathways.132 |
| miR-212 | Modulates the Wnt/β-catenin, Hedgehog, and Hippo/YAP signaling pathways.136 |
| miR-320 | Suppresses E-cadherin level and increases N-cadherin and vimentin expression by directly targeting FOXM1; regulates the Wnt, PI3K/AKT, TGF-β/Smad, CDK6, STAT3, and E2F1 signaling pathways.139 |
| miR-335 | Targets the Hedgehog, the PI3K/AKT/mTOR, and the Hippo/YAP signaling pathways.140 |
| miR-375 | Targets the AEG-1, YAP1, IGF-1R, PDK1, Wnt, NF-κB, Notch, and TGF-β/Smad signaling pathways.141,142 |
| miR-449a | Targets the TAK1, Notch, NF-κB/p65/VEGF, RB-E2F, MAPKs, Wnt/β-catenin, p53, and androgen receptor signaling pathways.143 |
| miR-802 | Modulates the regulation of the Wnt, PI3K/AKT, ERK, and Hedgehog signaling pathways.144 |
AEG-1, astrocyte elevated gene 1; AKT, protein kinase B; APC, adenomatous polyposis coli; BCL2, B-cell lymphoma 2; CCND1, cyclin D1; CDK6, cyclin dependent kinase 6; EGFR, epidermal growth factor receptor; ERK, extracellular receptor kinase; FOX, forkhead box; GSK3β, glycogen synthase kinase-3β; HIF1, hypoxia-inducible factor 1; IGF-1R, insulin-like growth factor 1 receptor; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; MCL1, induced myeloid leukemia cell differentiation protein; miRNA, microRNA; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappa B; PDCD4, programmed cell death protein 4; PDK1, phosphoinositide-dependent kinase-1; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; Ras, rat sarcoma virus; RB, retinoblastoma-like protein; RECK, reversion-inducing cysteine-rich protein with Kazal motifs; Smad, small mother against decapentaplegic; Src, steroid receptor coactivator; STAT, signal transducer activator of transcription; TAK1, TGF-β activated kinase 1; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; XRCC2, X-ray repair complementing defective repair gene; YAP, yes-associated protein.