Table 4.
LncRNA-mediated regulation of glutathione metabolic pathways in cancer.
| lncRNA | Target | Redox Enzymes Affected | GSH Level | Oxidative Stress | Cancer Type | Regulation | Effect | Ref |
|---|---|---|---|---|---|---|---|---|
| H19 | NRF2 | NQO1, GR, G6PD, GCLC, GCLM, GSTP1 | ↓ (upon H19 knockdown) | ↑ (upon H19 knockdown) | Multiple cancers | Transcriptional regulation of NRF2 targets | Promotes antioxidant defense, cancer progression | [176] |
| LINC00493 | AGK, SLC25A11 | – | Maintain mitoGSH import | – | ccRCC | Binds AGK and SLC25A11 via N-terminus | Inhibits cancer metastasis. | [178] |
| PVT1 | STAT3/GPX4 axis; miR-214–3p/GPX4 axis | GPX4 | ↓ (when PVT1 inhibited) | ↑ (when PVT1 inhibited) | OS; HCC | Activates STAT3 signaling and upregulates GPX4; Sponges miR-214–3p and upregulates GPX4 |
Inhibits ferroptosis, promotes proliferation/metastasis | [179,187] |
| XLOC_009190 | MGST1 | MGST1 | Potentially modulates (via MGST1 activity) | – | Lung adenocarcinoma | Cis-regulation of MGST1; trans-regulation of GPCRs/potassium channels | Participate in cellular protection via GSH conjugation | [180] |
| MSTRG51053.2 | miR-432–5p/MGST3 | MGST3, MGST1, GST-ω1 | ↑ (implied by ↑ MGST3/GST activity) | ↓ (implied by ↑ detoxification) | NSCLC | ceRNA to sponge miR-432–5p, upregulating MGST3 | Promotes cisplatin resistance | [181] |
| LncRNA ROR | p53 | SOD | ↓ (upon ATO treatment) | ↑ | HCC | Induced by ATO via oxidative stress, sponges/represses p53 expression | Confers ATO resistance | [182] |
| lnc-AP (encodes pep-AP) | TALDO1 | TALDO1 | ↓ | ↑ | CRC | pep-AP binds and suppresses TALDO1, attenuates PPP, inhibits NADPH/GSH | Sensitizes CRC to oxaliplatin | [183] |
| NUTM2A-AS1 | miR-613/VEGFA | SOD | ↑ | ↓ | GC | Sponges miR-613, upregulates VEGFA, modulates redox balance | Confers matrine resistance | [184] |
| VPS9D1-AS1 | miR-491–5p/miR-214–3p/GPX1 | GPX1 | ↑ (implied by ↓ GPX1-mediated GSH consumption) | ↓ | ALL | Acts as a ceRNA to sponge miR-491–5p/miR-214–3p and upregulates GPX1 | Promotes ALL progression | [186] |
| NEAT1 | miR-362–3p/MIOX | MIOX | ↓ | ↑ | HCC | NEAT1 sponges miR-362–3p and upregulates MIOX | Promotes ferroptosis, sensitizes HCC to erastin/RSL3 | [188] |
| PMAN | ELAVL1/SLC7A11 | – | ↑ | ↓ | GC | PMAN binds ELAVL1, stabilizes SLC7A11 mRNA | Inhibits ferroptosis, Promoting PM survival under hypoxia | [189] |
| CASC2 | FMR1/SOCS2/SLC7A11 | GPX4 | ↓ | ↑ | GC | CASC2 stabilizes SOCS2 mRNA and ubiquitinates SLC7A11 | Promotes ferroptosis | [190] |
| HCP5 | GPX4 | GPX4 | ↑ (implied by GPX4-mediated GSH recycling) | ↓ | TNBC | Encoded protein HCP5-132aa upregulates GPX4 expression | Promotes TNBC progression | [191] |
| LINC00618 | LSH/SLC7A11/BAX | – | ↓ | ↑ | Leukemia | Downregulates LSH and SLC7A11 transcription; upregulates BAX/caspase-3 | Dual pro-death role | [192] |
| GSEC | miR-101–3p/CISD1/ATP5MC3/PGD | – | ↑ (implied by GSH metabolism) | – | LUAD | Sponges miR-101–3p and upregulates CISD1/ATP5MC3/PGD; activates ferroptosis/glutathione pathways | Promotes LUAD progression | [193] |
| CASC11 | SLC7A11 | – | ↑ | ↓ | HCC | Binds/stabilizes SLC7A11 mRNA, upregulates SLC7A11 protein expression | Inhibits sorafenib-induced ferroptosis | [194] |
| SLC7A11-AS1 | xCT | GCLM | ↓ | ↑ | GC | Directly suppressed xCT expression, low SLC7A11-AS1 activated expression of GCLM | Sensitizes GC to cisplatin | [195] |
| GDIL | CHAC1 | CHAC1 | ↑ | ↓ | CRC, ovarian cancer | re-localizes XRN2 protein to cytoplasm, XRN2 further degrades CHAC1 mRNA | Induces platinum resistance | [196] |
| MT1DP | miR-365a-3p/NRF2 | NRF2-regulated enzymes (e.g., HO-1, NQO1) | ↓ | ↑ | NSCLC | Stabilizes miR-365a-3p and downregulates NRF2 | Promotes ferroptosis | [111] |
| LINC01419 | GSTP1 promoter | GSTP1 | ↑ (implied by GSTP1 suppression) | – | ESCC | Binds GSTP1 promoter, recruits DNMTs, hypermethylates GSTP1, downregulates GSTP1 expression | Promotes ESCC progression | [197] |
| LINC01270 | GSTP1 promoter | GSTP1 | ↑ (implied by GSTP1 suppression) | – | EC | Recruits DNMT1/DNMT3A/DNMT3B, hypermethylates GSTP1 promoter, downregulates GSTP1 expression | Promotes EC progression | [198] |
| ITGB2-AS1 | FOSL2/NAMPT/p53 | GPX4 | ↑ | ↓ | NSCLC | Binds FOSL2, upregulates NAMPT, NAMPT inhibits p53, inhibits ferroptosis | Promotes cisplatin resistance | [199] |
| LINC01134 | Nrf2/GPX4 | GPX4 | ↓ GSH/GSSG ratio | ↑ | HCC | Promotes Nrf2 binding to GPX4 promoter, enhances GPX4 transcription | Confers oxaliplatin resistance | [200] |
| AFAP1-AS1 | Wnt/β-catenin pathway | – | ↑ | ↓ | TNBC | Activates Wnt/β-catenin signaling | Promotes radioresistance | [201] |
NRF2, Nuclear factor erythroid 2-related factor 2; NQO1, NAD(P)H quinone dehydrogenase 1; GR, Glutathione reductase; G6PD, Glucose-6-phosphate dehydrogenase; GCLC, Glutamate-cysteine ligase catalytic subunit; GCLM, Glutamate-cysteine ligase modifier subunit; GSTP1, Glutathione S-transferase pi 1; AGK, Acylglycerol kinase; SLC25A11, Solute carrier family 25 member 11 (mitochondrial 2-oxoglutarate/malate carrier); ccRCC, Clear cell renal cell carcinoma; PVT1, Plasmacytoma variant translocation 1; STAT3, Signal transducer and activator of transcription 3; GPX4, Glutathione peroxidase 4; OS, Osteosarcoma; HCC, Hepatocellular carcinoma; MGST1, Microsomal glutathione S-transferase 1; GPCRs, G protein-coupled receptors; NSCLC, Non-small cell lung cancer; ATO, Arsenic trioxide; TALDO1, Transaldolase 1; CRC, Colorectal cancer; PPP, Pentose phosphate pathway; NADPH, Nicotinamide adenine dinucleotide phosphate; NUTM2A-AS1, NUT family member 2A antisense RNA 1; GC, Gastric cancer; VEGFA, Vascular endothelial growth factor A; ALL, Acute lymphoblastic leukemia; NEAT1, Nuclear paraspeckle assembly transcript 1; MIOX, Myo-inositol oxygenase; ELAVL1, ELAV like RNA binding protein 1 (HuR); CASC2, Cancer susceptibility candidate 2; SOCS2, Suppressor of cytokine signaling 2; HCP5, HLA complex P5; TNBC, Triple-negative breast cancer; LSH, Lymphoid-specific helicase; GSEC, Gastric cancer survival-associated enhancer RNA; LUAD, Lung adenocarcinoma; CASC11, Cancer susceptibility candidate 11; SLC7A11, Solute carrier family 7 member 11 (xCT); GDIL, GSH Degradation Inhibiting LncRNA; CHAC1, ChaC glutathione specific gamma-glutamylcyclotransferase 1; XRN2, 5′-3′ exoribonuclease 2; MT1DP, Metallothionein 1D pseudogene; HO-1, Heme oxygenase 1; ESCC, Esophageal squamous cell carcinoma; DNMTs, DNA methyltransferases; EC, Esophageal cancer; ITGB2-AS1, Integrin subunit beta 2 antisense RNA 1; FOSL2, FOS like 2, AP-1 transcription factor subunit; NAMPT, Nicotinamide phosphoribosyltransferase; AFAP1-AS1, Actin filament associated protein 1 antisense RNA 1; NP, Nanoparticle; siRNA, Small interfering RNA; GSH, Glutathione; ROS, Reactive oxygen species; MDA, Malondialdehyde; ceRNA, Competing endogenous RNA; GSSG, Oxidized glutathione.