Relationship between miRNA and ferroptosis in tumors

Abstract

Malignant tumor is a major killer that seriously endangers human health. At present, the methods of treating tumors include surgical resection, chemotherapy, radiotherapy and immunotherapy. However, the survival rate of patients is still very low due to the complicated mechanism of tumor occurrence and development and high recurrence rate. Individualized treatment will be the main direction of tumor treatment in the future. Because only by understanding the molecular mechanism of tumor development and differentially expressed genes can we carry out accurate treatment and improve the therapeutic effect. MicroRNA (miRNA) is a kind of small non coding RNA, which regulates gene expression at mRNA level and plays a key role in tumor regulation. Ferroptosis is a kind of programmed death caused by iron dependent lipid peroxidation, which is different from apoptosis, necrosis and other cell death modes. Now it has been found that ferroptosis plays an important role in the occurrence and development of tumors and drug resistance. More and more studies have found that miRNAs can regulate tumor development and drug resistance through ferroptosis. Therefore, in this review, the mechanism of ferroptosis is briefly outlined, and the relationship between miRNAs and ferroptosis in tumors is reviewed.

Keywords: ferroptosis; invasion; mechanism; metastasis; microRNA; proliferation; sensitivity of treatment; tumor.

FIGURE 1

The regulatory mechanism of ferroptosis. The regulatory network of ferroptosis is mainly divided into two categories: Oxidation system and antioxidant system. The oxidation system includes iron metabolism, lipid metabolism, glutamate metabolism, etc. The antioxidant system includes system xc⁻/GSH/GPX4 axis, FSP1/CoQ10/NAD (P) H axis, GCH1/BH4 axis, etc. Iron metabolism: Transferrin (TF); Transferrin receptor 1 (TFRC); Six transmembrane epithelial antigen of protein 3 (STEAP3); Divalent metal ion transporter 1 (DMT1); Zinc transporter 8/14 (ZIP8/14); Labile iron pool (LIP); ferroportin (FPN); Ferritin heavy chain 1 (FTH1); Ferritin light chain (FTL); Solute carrier family member 11A2 (SLC11A2); Iron response element binding protein 2 (IREB2); Reactive oxygen species (ROS); Poly (RC) binding protein 2 (PCBP2); Nuclear receptor coactivator 4 (NCOA4); Multivesicular bodies (MVB). Lipid metabolism: Polyunsaturated fatty acid (PUFA); Long chain acyl CoA synthetase 4 (ACSL4); Lysophosphatidylcholine acyltransferase 3 (LPCAT3); Phosphatidylethanolamine (PE); Arachidonic acid lipid peroxidase (ALOX). Glutamate metabolism: Glutamine transporter (SLC1A5); Glutamic acid cysteine ligase 1 (GCL1); Glutamic acid cysteine ligase 2 (GCL2); Glutamic-oxaloacetic transaminase 1 (GOT1); α- Ketoglutarate (α KG). Tricarboxylic acid cycle (TCA cycle). System xc^-/GSH/GPX4 axis: Cystine/glutamate antiporter (system xc⁻); Solute carrier family member 7A11 (SLC7A11); Solute carrier family member 3A2 (SLC3A2); Glutathione (GSH); Thioredoxin reductase 1 (TXNRD1); Glutamic acid cysteine ligase (GCL); Glutathione synthetase (GSS); Glutathione peroxidase 4 (GPX4); oxidized glutathione (GSSG); Selenium (Se). FSP1/CoQ10/NAD (P) H axis: ferroptosis suppressor protein 1 (FSP1); Oxidized coenzyme Q10 (CoQ10); Reduced coenzyme Q10 (CoQ10H₂). 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA); 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR); Mevalonate (MVA); Isopentenyl pyrophosphate (IPP); Farnesyl pyrophosphate (FPP); Geranylgeranyl pyrophosphate (GGPP). GCH1/BH4 axis: Guanosine triphosphate (GTP); GTP cyclohydrolase 1 (GCH1); Tetrahydrobiopterin (BH4); Other regulatory factors: Nuclear factor E2 related factor 2 (NRF2); Heme oxygenase 1 (HO-1); NAD (P) H-dependent quinone oxidoreductase 1 (NQO1); Kelch like ECH associated protein 1 (KEAP1); Cullin3 (CUL3); Activating transcription factor 4 (ATF4); Activating transcription factor 4 (ATF4); OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1); Beclin1(BECN1); AMP activated protein kinase (AMPK); BRCA1 related protein 1 (BAP1); Histone 2A ubiquitination (H2AUB); Yes associated protein 1 (YAP1); Signal transducer and activator of transcription 3 (STAT3).