Exploiting Interdata Relationships in Prostate Cancer Proteomes : Clinical Significance of HO-1 Interactors
Prostate cancer (PCa) cells display abnormal expression of proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown the anti-tumoral role of heme oxygenase 1 (HO-1) in this disease. In this work, we undertook a mass spectrometry-based proteomics study to identify HO-1 molecular interactors that might collaborate with its modulatory function in PCa. Among the HO-1 interactors, we identified proteins with nuclear localization. Correlation analyses, using the PCa GSE70770 dataset, showed a significant and positive correlation between HMOX1 and 6 of those genes. Alternatively, HMOX1 and YWHAZ showed a negative correlation. Univariable analyses evidenced that high expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with increased relapse-free survival (RFS) in PCa patients. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, a decrease in RFS for patients with higher scores of this signature was observed using a prognostic risk score model. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. Multivariable analyses confirmed HSPB1, DDB1, and YWHAZ independence from PCa clinic-pathological parameters. In parallel, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (protein encoded by YWHAZ) interaction. Herein, we describe a novel protein interaction between HO-1 and 14-3-3ζ/δ in PCa and highlight these factors as potential therapeutic targets.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Antioxidants (Basel, Switzerland) - 11(2022), 2 vom: 31. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lage-Vickers, Sofia [VerfasserIn] |
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| Links: |
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| Themen: |
HMOX1 |
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| Anmerkungen: |
Date Revised 18.04.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/antiox11020290 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM337357250 |
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| 520 | |a Prostate cancer (PCa) cells display abnormal expression of proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown the anti-tumoral role of heme oxygenase 1 (HO-1) in this disease. In this work, we undertook a mass spectrometry-based proteomics study to identify HO-1 molecular interactors that might collaborate with its modulatory function in PCa. Among the HO-1 interactors, we identified proteins with nuclear localization. Correlation analyses, using the PCa GSE70770 dataset, showed a significant and positive correlation between HMOX1 and 6 of those genes. Alternatively, HMOX1 and YWHAZ showed a negative correlation. Univariable analyses evidenced that high expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with increased relapse-free survival (RFS) in PCa patients. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, a decrease in RFS for patients with higher scores of this signature was observed using a prognostic risk score model. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. Multivariable analyses confirmed HSPB1, DDB1, and YWHAZ independence from PCa clinic-pathological parameters. In parallel, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (protein encoded by YWHAZ) interaction. Herein, we describe a novel protein interaction between HO-1 and 14-3-3ζ/δ in PCa and highlight these factors as potential therapeutic targets | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HMOX1 | |
| 650 | 4 | |a YWHAZ | |
| 650 | 4 | |a prostate cancer | |
| 650 | 4 | |a protein interactions | |
| 650 | 4 | |a proteomics | |
| 650 | 4 | |a transcriptomics | |
| 700 | 1 | |a Sanchis, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Bizzotto, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Toro, Ayelen |e verfasserin |4 aut | |
| 700 | 1 | |a Sabater, Agustina |e verfasserin |4 aut | |
| 700 | 1 | |a Lavignolle, Rosario |e verfasserin |4 aut | |
| 700 | 1 | |a Anselmino, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Labanca, Estefania |e verfasserin |4 aut | |
| 700 | 1 | |a Paez, Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a Navone, Nora |e verfasserin |4 aut | |
| 700 | 1 | |a Valacco, Maria P |e verfasserin |4 aut | |
| 700 | 1 | |a Cotignola, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Vazquez, Elba |e verfasserin |4 aut | |
| 700 | 1 | |a Gueron, Geraldine |e verfasserin |4 aut | |
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