Table 2.

miRNA-Mediated GSH Regulation in Cancer.

miRNA	Target	Redox Enzymes Affected	GSH Level	Oxidative Stress	Cancer Type	Regulation	Effect	Ref
miR-433	GCLC, GCLM	GCLC, GCLM	↓	↑	Various cancers	Inhibits GSH synthesis	Reduces antioxidant capacity	[104]
miR-18a	GCLC	GCLC	↓	↑	Liver cancer	MYC-induced suppression of GSH synthesis	Enhances oxidative stress sensitivity	[105]
miR-125b	PCTP, LIPA and GSS	GSS	↑	↓	Chronic lymphocytic leukemia (CLL)	Regulates transcripts encoding enzymes and factors in metabolism	Promotes tumor survival and therapy resistance	[109]
miR-34a	NRF2	–	↑	↓	Colorectal cancer	Enhances antioxidant defenses	Promotes tumor growth and chemotherapy resistance	[110]
miR-365a-3p	NRF2	HO-1, NQO1	↓	↑	NSCLC	Disrupts antioxidant defenses	Promotes chemoresistance	[111]
miR-153	NRF2 GPX1	GPx1	↓	↑	Glioma	Disrupts antioxidant defenses	Promotes stemness and radioresistance	[112]
miR-23a/b	Mitochondrial GLS	GLS	↑ (implied by reduced glutamate availability)	↓	B-cell lymphoma, Prostate cancer	Suppresses glutamine catabolism	Promotes proliferation	[113]
miR-203	GLS	GLS	↑ (implied by reduced glutamate availability)	↓	MM	Suppresses glutamine metabolism	Promotes chemosensitivity	[114]
miR-21	SOD3, TNF-α, SOD2	SOD3, SOD2	–	↑O2•- ↓ H2O2 conversion	Pan-cancer	Disrupts ROS metabolism	Promotes tumorigenesis	[116]
miR-5096	SLC7A11	–	↓	↑	Breast cancer	Reduces cystine uptake, lowering GSH	Promotes ferroptosis, inhibits tumor growth	[119]
miR-506–3p	GSTP1	GST	↓	↑	CRC	Suppresses GSTP1, reducing GSH conjugation	Increases chemotherapy sensitivity	[120]
miR-214–3p	ATF4 GR SLC3A2	GR COX2, ACSL4, PTGS2, GPX4, NOX1	↓	↑	HCC	Inhibits ATF4-mediated antioxidant response, downregulates SLC3A2	Promotes ferroptosis, inhibits tumor growth	[123,129,130]
miR-103a-2-5p	LILRB3	Nrf2, HO-1	↓	↑	AML	Downregulates LILRB3	Inhibits AML cell proliferation, reduces CD8+ T cell apoptosis, suppresses tumor growth	[126]
miR-185–5p	GPX1	GPX1	↑ (implied by GPX1 ↓)	↓	AML	Downregulates GPX1	Blocks AML progression	[127]
miR-6085	AIFM2, GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	HCC	Directly targets AIFM2 & GPX4	Promotes ferroptosis, inhibits HCC progression	[128]
miR-1231	GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	PTC	Directly targets GPX4, inducing ferroptosis	Inhibits cancer progression	[131]
miR-188–3p	GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	OS	Directly targets GPX4, inducing ferroptosis	Inhibits cancer progression	[132]
miR-1287–5p	GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	OS	Downregulates GPX4, inducing ferroptosis	Suppresses tumor progression	[133]
miR-26b-5p	MAT2A	–	↓	↑	OS	Directly targets MAT2A, activates STAT3/SLC7A11signaling	Suppresses tumor proliferation/invasion	[134]
miR-144–3p	ZEB1	GPX4	↓ (implied by ↑ ferroptosis)	↑	OS	Directly targets ZEB1, inducing ferroptosis	Suppresses tumor proliferation/migration/invasion	[135]
miR-128–3p	SP1/CD98hc	GPX4	↓ (implied by ↑ ferroptosis)	↑	Breast Cancer	Negatively regulates GPX4, inducing ferroptosis	Suppresses tumor migration/invasion/stemness	[136]
miR-15a-3p	GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	CRC	Negatively regulates GPX4	Induces ferroptosis	[137]
miR-634	GPX4	GPX4	↓ (implied by ↑ ferroptosis)	↑	PC	Negatively regulates GPX4	Induces ferroptosis	[138]
miR-34c-3p	SLC7A11	GPX4	↓ (implied by ↑ ferroptosis)	↑	OSCC	Negatively regulates GPX4	Induces ferroptosis	[216]
miR-26a-5p	SLC7A11	GPX4	↓ (implied by ↑ ferroptosis)	↑	OSCC	Negatively regulates GPX4	Induces ferroptosis	[140]
miR-122–5p	CS	–	↓	↑	NPC	Negatively regulates CS	Induces ferroptosis	[141]
miR-133b	GSTP1	GST	↓	–	NSCLC	Negatively regulates GSTP1	Inhibits cisplatin resistance and tumor progression	[143]
miR-497	TKT	pentose phosphate pathway	↓	↑	Cervical cancer	Negatively regulates TKT	Inhibits cisplatin resistance	[144]
miR-195–5p	PLAG1, PVT1	GPX4	↓ (implied by ↑ ferroptosis)	↑	HCC	Negatively regulates PLAG1/PVT1	Induces ferroptosis	[147]
miR-15b-3p	KLF2	GPX4	↑ (implied by ↑ ferroptosis)	↓	PCa	Negatively regulates KLF2	Inhibits ferroptosis, promotes BIC resistance	[148]
miR-7-5p	ACVRL1	GPX2	↑ (implied by GPX2 ↑)	↓	CRC	Downregulated by the Wnt/β-catenin/TCF-1-KCNQ1OT1 axis	Inhibition of miR-7-5p promotes resistance to mTKIs	[150]

GCLC, Glutamate-cysteine ligase catalytic subunit; GCLM, Glutamate-cysteine ligase modifier subunit; GSS, Glutathione synthetase; NRF2, Nuclear factor erythroid 2-related factor 2; HO-1, Heme oxygenase-1; NQO1, NAD(P)H quinone dehydrogenase 1; GPX1, Glutathione peroxidase 1; GLS, Glutaminase; SOD3, Superoxide dismutase 3; SOD2, Superoxide dismutase 2; TNF-α, Tumor necrosis factor-alpha; SLC7A11, Solute carrier family 7 member 11 (cystine/glutamate transporter, xCT); GST, Glutathione S-transferases; GSTP1, Glutathione S-transferase Pi 1; ATF4, Activating transcription factor 4; GR, Glutathione reductase; SLC3A2, Solute carrier family 3 member 2 (CD98 heavy chain); COX2, Cyclooxygenase-2; ACSL4, Acyl-CoA synthetase long-chain family member 4; PTGS2, Prostaglandin-endoperoxide synthase 2; NOX1, NADPH oxidase 1; LILRB3, Leukocyte immunoglobulin-like receptor subfamily B member 3; AIFM2, Apoptosis-inducing factor mitochondria-associated 2; PTC, Papillary thyroid carcinoma; OS, Osteosarcoma; MAT2A, Methionine adenosyltransferase 2A; STAT3, Signal transducer and activator of transcription 3; ZEB1, Zinc finger E-box binding homeobox 1; SP1, Specificity protein 1; CD98hc, CD98 heavy chain (SLC3A2); PC, Pancreatic cancer; OSCC, Oral squamous cell carcinoma; CS, Citrate synthase; NPC, Nasopharyngeal carcinoma; TKT, Transketolase; PLAG1, Pleomorphic adenoma gene 1; PVT1, Plasmacytoma variant translocation 1; KLF2, Kruppel-like factor 2; PCa, Prostate cancer; BIC, Bicalutamide; CRC, Colorectal cancer; mTKIs, Multitarget tyrosine kinase inhibitors; ROS, Reactive oxygen species; GSH, Glutathione; NSCLC, Non-small cell lung cancer; HCC, Hepatocellular carcinoma; MM, Multiple myeloma; AML, Acute myeloid leukemia; CLL, Chronic lymphocytic leukemia.