Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Establishment of Prx4−/− Mice and Prx4−/−/Srx−/− Mice
2.2. Urethane-Induced Mouse Lung Cancer Protocol and Tissue Processing
2.3. Cell Culture and Establishment of Stable Knockdown Cells
2.4. Intracellular ROS Level Measurement
2.5. Immunoblotting
2.6. Bioinformatics Analysis
2.6.1. Data Source
2.6.2. Expression Analysis of Prx4
2.6.3. Clinical Correlation Analysis
2.6.4. Functional Enrichment Analysis of PRX4
2.6.5. Immune Infiltration Analysis
2.6.6. Investigation of the Bio-Mechanisms of Aberrant Prx4 Expression
2.7. Statistical Evaluation
3. Results
3.1. Loss of Prx4 or Srx/Prx4 Inhibits Tumor Formation and Cell Proliferation
3.2. Depletion of Prx4 or Prx4/Srx Reduces Intratumoral Macrophage Infiltration
3.3. Exposure to Urethane Activates Srx and Prx4 Expression Which Contributes to Cell Transformation
3.4. Bioinformatics Analysis of Prx4
3.4.1. Prx4 Is Significantly Upregulated in LUAD Patients and Is Negatively Correlated with Patient Survival and Prognosis
3.4.2. Prx4 May Affect the Tumor Microenvironment of LUAD
3.4.3. Investigation of the Biological Mechanism of Abnormal Expression of PRX4
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Features | H_Prx4 (n = 409) | L_PRDX4 (n = 88) | p Value |
---|---|---|---|
age | 0.01047 | ||
age < 65 | 190 | 28 | |
age ≥ 65 | 213 | 56 | |
pathologic_M | 0.3475 | ||
M0 | 278 | 53 | |
M1 | 19 | 5 | |
pathologic_N | 0.473 | ||
N0 | 259 | 62 | |
N1 | 82 | 12 | |
N2 | 58 | 11 | |
N3 | 2 | 0 | |
pathologic_T | 0.01243 | ||
T1 | 131 | 35 | |
T2 | 227 | 40 | |
T3 | 36 | 7 | |
T4 | 15 | 3 | |
tobacco_smoking_history | 0.7146 | ||
NO | 56 | 15 | |
YES | 341 | 71 | |
gender | 0.7899 | ||
female | 223 | 46 | |
male | 186 | 42 | |
tissue_or_origin | 0.6715 | ||
Lower lobe | 137 | 31 | |
Middle lobe | 17 | 4 | |
Upper lobe | 239 | 52 | |
tumor_stage | 0.6122 | ||
stage i | 216 | 51 | |
stage ii | 102 | 16 | |
stage iii | 66 | 14 | |
stage iv | 19 | 6 |
Cell | Gene | r | p Value | Q Value |
---|---|---|---|---|
B cells memory | Prx4 | −0.0357658 | 0.39488518 | 0.39488518 |
Plasma cells | Prx4 | 0.40876086 | 2.75 × 10−24 | 1.93 × 10−23 |
T cells CD4 memory activated | Prx4 | 0.18108563 | 1.41 × 10−5 | 1.97 × 10−5 |
T cells gamma delta | Prx4 | 0.20982468 | 4.51 × 10−7 | 7.90 × 10−7 |
Monocytes | Prx4 | −0.2933115 | 9.86 × 10−13 | 3.45 × 10−12 |
Macrophages M2 | Prx4 | −0.1713956 | 4.13 × 10−5 | 4.81 × 10−5 |
Mast cells resting | Prx4 | −0.2319601 | 2.24 × 10−8 | 5.22 × 10−8 |
miRNA ID | miRNA Name | geneID | Gene Name | Gene Type | Chromosome | Narrow Start | Narrow End | Broad Start | Broad End | Strand | clipExp Num | DegraExp Num | PITA | RNA22 | miRmap | microT | miRanda | Pancancer Num |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MIMAT0000449 | hsa-miR-146a-5p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704483 | 23704489 | 23704469 | 23704490 | + | 5 | 0 | 1 | 0 | 1 | 0 | 1 | 6 |
MIMAT0001631 | hsa-miR-451a | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704500 | 23704505 | 23704485 | 23704506 | + | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 1 |
MIMAT0002178 | hsa-miR-487a-3p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704470 | 23704475 | 23704470 | 23704475 | + | 5 | 0 | 1 | 0 | 0 | 0 | 0 | 6 |
MIMAT0002809 | hsa-miR-146b-5p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704483 | 23704489 | 23704466 | 23704490 | + | 5 | 0 | 1 | 0 | 1 | 0 | 1 | 3 |
MIMAT0002824 | hsa-miR-498 | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704476 | 23704482 | 23704476 | 23704482 | + | 4 | 0 | 1 | 0 | 1 | 0 | 0 | 4 |
MIMAT0003245 | hsa-miR-580-3p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704485 | 23704490 | 23704485 | 23704490 | + | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 2 |
MIMAT0004793 | hsa-miR-556-3p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23693402 | 23693407 | 23693402 | 23693407 | + | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 3 |
MIMAT0004799 | hsa-miR-589-5p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23704484 | 23704489 | 23704484 | 23704489 | + | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 3 |
MIMAT0015037 | hsa-miR-3163 | ENSG00000123131 | Prx4 | protein_coding | chrX | 23693418 | 23693446 | 23693418 | 23693446 | + | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
MIMAT0018204 | hsa-miR-676-3p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23693424 | 23693452 | 23693424 | 23693452 | + | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
MIMAT0019062 | hsa-miR-4524a-5p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23693414 | 23693420 | 23693393 | 23693421 | + | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
MIMAT0022255 | hsa-miR-4524b-5p | ENSG00000123131 | Prx4 | protein_coding | chrX | 23693414 | 23693420 | 23693393 | 23693421 | + | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
HR | Lower.95 | Upper.95 |
---|---|---|
hsa-miR-146a-5p | 0.91033546 | 0.79799012 |
hsa-miR-146b-5p | 0.94493836 | 0.81559882 |
hsa-miR-3163 | 12.3304215 | 2.93772613 |
hsa-miR-451a | 0.98124854 | 0.8963051 |
hsa-miR-4524a-5p | 0.84779499 | 0.35083517 |
hsa-miR-4738-3p | 0.85010695 | 0.53104859 |
hsa-miR-487a-3p | 1.10794343 | 0.95751824 |
hsa-miR-556-3p | 0.86824518 | 0.68867783 |
hsa-miR-580-3p | 0.86960466 | 0.65553948 |
hsa-miR-589-5p | 1.04741951 | 0.86650936 |
hsa-miR-676-3p | 0.9633758 | 0.78058721 |
hsa-miR-708-3p | 0.98595142 | 0.86659775 |
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Hao, Y.; Jiang, H.; Thapa, P.; Ding, N.; Alshahrani, A.; Fujii, J.; Toledano, M.B.; Wei, Q. Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer. Antioxidants 2023, 12, 367. https://doi.org/10.3390/antiox12020367
Hao Y, Jiang H, Thapa P, Ding N, Alshahrani A, Fujii J, Toledano MB, Wei Q. Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer. Antioxidants. 2023; 12(2):367. https://doi.org/10.3390/antiox12020367
Chicago/Turabian StyleHao, Yanning, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, and Qiou Wei. 2023. "Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer" Antioxidants 12, no. 2: 367. https://doi.org/10.3390/antiox12020367
APA StyleHao, Y., Jiang, H., Thapa, P., Ding, N., Alshahrani, A., Fujii, J., Toledano, M. B., & Wei, Q. (2023). Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer. Antioxidants, 12(2), 367. https://doi.org/10.3390/antiox12020367