Table 1.
MicroRNA targets multiple ROS signaling pathways in cancer.
| MicroRNAs | Targets | Mechanism | Relevant cancer | Ref. |
|---|---|---|---|---|
| miR-28 | Nrf2/Keap1 pathway | Nrf2 downregulation; colony formation | Breast cancer | [24] |
| miR-200a | Nrf2/Keap1 pathway | Keap1 downregulation; Nrf2 activation | Breast cancer; hepatocellular carcinoma | [25, 101, 102] |
| miR-144 | Nrf2/Keap1 pathway | Regulate the cisplatin resistance of lung cancer cells via Nrf2 | Lung cancer | [103] |
| miR-93 | Nrf2/Keap1 pathway | Downregulating Nrf2 and Nrf2-related genes | Breast cancer | [23] |
| miR-155 | Nrf2/Keap1 pathway | Bach1 downregulation; upregulation of HO-1; enhance resistance to oxidative stress | Renal cancer; lung cancer | [26, 104, 105] |
| miR-125b | Nrf2/Keap1 pathway | Targeting the anti-oxidative gene PRXL2A | Oral squamous cell carcinoma | [27] |
| miR-29 | Mitochondrial pathway | Promoting apoptosis through a mitochondrial pathway that involves Mcl-1 and Bcl-2 | Hepatocellular carcinoma | [106] |
| miR-34a | Mitochondrial pathway | Inhibiting tumor growth and inducing apoptosis | Multiple myeloma | [33] |
| miR-30a | Mitochondrial pathway | Downregulating Beclin 1 and ATG5 expression; inhibiting autophagy | Chronic myeloid leukemia | [107] |
| miR-122 | Mitochondrial pathway | Targeting mitochondrial metabolic genes | Hepatocellular carcinoma | [108] |
| miR-375 | Mitochondrial pathway | Reducing expression of ATG7; inhibiting autophagy | Hepatocellular carcinoma | [109] |
| miR-450a | Mitochondrial pathway | Suppressing multiple genes involved in the EMT; targeting glutaminolysis related genes; reducing tumor migration and invasion | Ovarian cancer | [34] |
| miR-27b | Mitochondrial pathway | Suppressing PDHX; reducing mitochondrial oxidation and promoting extracellular acidification; promoting cell proliferation | Breast cancer | [110] |
| miR-31 | Mitochondrial pathway | Inhibiting SIRT3; promoting tumor migration and invasion | Oral carcinoma | [36] |
| mitomiR-2392 | Mitochondrial pathway | Reprogramming metabolism by downregulation of oxidative phosphorylation and upregulation of glycolysis; regulating chemoresistance | Tongue squamous cell carcinoma | [37] |
| miR-17-3p | Mitochondrial pathway | Inhibiting Mn-SOD, Gpx2, and TrxR2; enhancing radiosensitivity | Prostate cancer | [38] |
| miR-128a | Mitochondrial pathway | Bmi-1 downregulation; maintain mitochondrial function and reduce ROS generation | Cancer | [111] |
| miR-210 | Mitochondrial pathway | ISCU downregulation; leading to upregulation of mitochondrial complex I activity and upregulation of mitochondrial ROS production | Cancer | [30, 112] |
| miR-663 | Mitochondrial pathway | Targeting BBC3 and BTG2; regulating apoptosis by controlling MOMP | Lung cancer | [113] |
| miR-3174 | Mitochondrial pathway | Targeting ARHGAP10; inhibiting mitochondria-dependent apoptosis and autophagy | Gastric cancer | [114] |
| miR-148a-3p | Mitochondrial pathway | Promoting mitochondrial fission and decreasing AKAP1 expression; sensitizing cisplatin treatment; suppressing RAB12 expression and mTOR1 activation | Gastric cancer | [115] |
| miR-485-3p, miR-485-5p | Mitochondrial pathway | Targeting and inhibiting the expression of PPARGC1A | Breast cancer | [116] |
| miR-195 | Mitochondrial pathway | Targeting ACACA, FASN, HMGCR, and CYP27B1; inhibiting proliferation, invasion and migration; decreasing mesenchymal markers expression and enhancing epithelial markers | Breast cancer | [117] |
| miR-21 | SOD/catalase pathway | Inhibiting T-AOC, PDCD4, SOD, and catalase | Gastric cancer | [118] |
| miR-146a | SOD/catalase pathway | Downregulating SOD2 and enhancing ROS generation; increasing apoptosis, inhibiting cell proliferation | Ovarian cancer; lung cancer | [47, 119] |
| miR-155 | SOD/catalase pathway | Increasing the level of SOD2 and catalase through inhibiting DCK; causing chemoresistance | Pancreatic cancer | [48] |
| miR-212 | SOD/catalase pathway | Targeting Mn-SOD; suppressing of Mn-SOD-induced metastasis | Colorectal cancer | [49] |
| miR-592 | HIF-1α pathway | miR-592/WSB1/HIF-1α axis inhibiting glycolytic metabolism | Hepatocellular carcinoma | [120] |
| miR-199a-5p | HIF-1α/COX-2 pathway | Regulating tumor growth and angiogenesis | Cancer | [121] |
| miR-135b | HIF-1α pathway | Promoting cancer cell proliferation, colony formation, survival, and angiogenesis through activation of HIF-1α | Head and neck squamous cell carcinoma | [122] |
| miR-138 | HIF-1α pathway | Suppressing cancer cell invasion and metastasis by targeting SOX4 and HIF-1α | Ovarian cancer | [123] |
| miR-186 | HIF-1α pathway | Inhibiting aerobic glycolysis | Gastric cancer | [124] |
| miR-206 | 14-3-3ζ/STAT3/HIF-1α/VEGF pathway | Decreasing the angiogenesis by targeting 14-3-3ζ and inhibiting the STAT3/HIF-1α/VEGF pathway | Lung cancer | [125] |
Nrf2: nuclear factor E2-related factor 2; Keap1: Kelch-like ECH-associated protein 1; HO-1: heme oxygenase-1; PRXL2A: peroxiredoxin-like 2A; ATG-5: autophagy-related 5; PDHX: pyruvate dehydrogenase complex component X; Mn-SOD: manganese superoxide dismutase; Gpx2: glutathione peroxidase 2; TrxR2: thioredoxin reductase 2; ISCU: iron-sulfur cluster assembly enzyme; BBC3: BCL2-binding component 3; BTG2: BTG antiproliferation factor 2; MOMP: mitochondrial outer membrane permeabilization; ARHGAP10: Rho GTPase-activating protein 10; AKAP1: A-kinase anchoring protein 1; PPARGC1A: PPARG coactivator 1 alpha; ACACA: acetyl-CoA carboxylase alpha; FASN: fatty acid synthase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; CYP27B1: cytochrome P450 family 27 subfamily B member 1; T-AOC: total antioxidation competence; SOD: superoxide dismutase; CAT: catalase; PDCD4: programmed cell death 4 protein; DCK: deoxycytidine kinase; WSB1: WD repeat and SOCS box containing 1; STAT3: signal transducer and activator of transcription 3; VEGF: vascular endothelial growth factor.