Crosstalk of MicroRNAs and Oxidative Stress in the Pathogenesis of Cancer

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.