Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study
Aim:The NRF2/KEAP1/p62/SQSTM1 pathway is the master regulator of antioxidant enzymes and detoxification proteins, both of which play a critical role in redox homeostasis. It shows that the this structurally active pathway has a crucial role in cancer as it inhibits tumorigenesis and metastatic proce...
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| Format: | Article |
| Language: | English |
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Galenos Yayincilik
2023-03-01
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| Series: | Namık Kemal Tıp Dergisi |
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http://namikkemalmedj.com/archives/archive-detail/article-preview/comparative-analysis-of-the-mutation-and-expressio/58941
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| author | Dilara Fatma AKIN Sedef Hande AKTAŞ |
| author_facet | Dilara Fatma AKIN Sedef Hande AKTAŞ |
| author_sort | Dilara Fatma AKIN |
| collection | DOAJ |
| description | Aim:The NRF2/KEAP1/p62/SQSTM1 pathway is the master regulator of antioxidant enzymes and detoxification proteins, both of which play a critical role in redox homeostasis. It shows that the this structurally active pathway has a crucial role in cancer as it inhibits tumorigenesis and metastatic processes and it induces pro-survival genes that promote chemoresistance. The relationship between the molecular mechanisms causing the pathway to malfunction and the development of brain tumors has yet to be fully clarified. The aim of this study is to analyze the genetic changes and expression level differences of the NRF2/KEAP1 pathway comparatively in low-grade gliomas (LGG) and glioblastoma multiforme (GBM) pathology.Materials and Methods:Gene expression profiles and DNA sequences of GBM (n=591) and LGG (n=511) patients and healthy tissue were downloaded from the TCGA database. Not only were gene expression and mutation patterns determined in this study, but also the impacts of genes on survival were assessed. PolyPhen-2 and SNAP tools were used to estimate the pathogenic properties of the changes identified.Results:A total of 16 mutations and gene amplification were identified in the KEAP1, NRF2, p62/SQSTM1, HMOX-1, and MOAP1 for both cancer groups, and the mutation carrying frequency was 4.6%. IDH1 p.R132H and NRF2 p.S164* mutation association was determined in 1 patient with LGG. KEAP1, NRF2, and HMOX1 expression levels for both LGG and GBM subtypes were determined to be high in patient samples compared to healthy samples (p<0.05).Conclusion:By targeting the NRF2/KEAP1/p62/SQSTM1 pathway anomalies, new therapeutic approaches can be provided in the treatment of glioma, particularly for chemotherapy sensitivity. |
| first_indexed | 2024-04-09T23:50:55Z |
| format | Article |
| id | doaj.art-f4439fd98e0941b59f2b7c811a3b64a5 |
| institution | Directory Open Access Journal |
| issn | 2587-0262 |
| language | English |
| last_indexed | 2024-04-09T23:50:55Z |
| publishDate | 2023-03-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | Namık Kemal Tıp Dergisi |
| spelling | doaj.art-f4439fd98e0941b59f2b7c811a3b64a52023-03-17T12:03:34ZengGalenos YayincilikNamık Kemal Tıp Dergisi2587-02622023-03-0111111110.4274/nkmj.galenos.2023.7474513049054Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico StudyDilara Fatma AKIN0Sedef Hande AKTAŞ1 Niğde Ömer Halisdemir Üniversitesi Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Niğde, Türkiye Eskişehir Osmangazi Üniversitesi, Translasyonel Tıp Araştırma ve Klinik Merkezi; Fen Bilimleri Enstitüsü, Biyoteknoloji ve Biyogüvenlik Anabilim Dalı; Sağlık Hizmetleri Meslek Yüksekokulu, Tıbbi Hizmetler ve Teknikler Anabilim Dalı, Eskişehir, Türkiye Aim:The NRF2/KEAP1/p62/SQSTM1 pathway is the master regulator of antioxidant enzymes and detoxification proteins, both of which play a critical role in redox homeostasis. It shows that the this structurally active pathway has a crucial role in cancer as it inhibits tumorigenesis and metastatic processes and it induces pro-survival genes that promote chemoresistance. The relationship between the molecular mechanisms causing the pathway to malfunction and the development of brain tumors has yet to be fully clarified. The aim of this study is to analyze the genetic changes and expression level differences of the NRF2/KEAP1 pathway comparatively in low-grade gliomas (LGG) and glioblastoma multiforme (GBM) pathology.Materials and Methods:Gene expression profiles and DNA sequences of GBM (n=591) and LGG (n=511) patients and healthy tissue were downloaded from the TCGA database. Not only were gene expression and mutation patterns determined in this study, but also the impacts of genes on survival were assessed. PolyPhen-2 and SNAP tools were used to estimate the pathogenic properties of the changes identified.Results:A total of 16 mutations and gene amplification were identified in the KEAP1, NRF2, p62/SQSTM1, HMOX-1, and MOAP1 for both cancer groups, and the mutation carrying frequency was 4.6%. IDH1 p.R132H and NRF2 p.S164* mutation association was determined in 1 patient with LGG. KEAP1, NRF2, and HMOX1 expression levels for both LGG and GBM subtypes were determined to be high in patient samples compared to healthy samples (p<0.05).Conclusion:By targeting the NRF2/KEAP1/p62/SQSTM1 pathway anomalies, new therapeutic approaches can be provided in the treatment of glioma, particularly for chemotherapy sensitivity. http://namikkemalmedj.com/archives/archive-detail/article-preview/comparative-analysis-of-the-mutation-and-expressio/58941 nrf2/keap1/p62/sqstm1 signaling pathwaygliomamutationgene expressionoxidative stress |
| spellingShingle | Dilara Fatma AKIN Sedef Hande AKTAŞ Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study Namık Kemal Tıp Dergisi nrf2/keap1/p62/sqstm1 signaling pathway glioma mutation gene expression oxidative stress |
| title | Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study |
| title_full | Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study |
| title_fullStr | Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study |
| title_full_unstemmed | Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study |
| title_short | Comparative Analysis of the Mutation and Expression Profile of the Cytoprotective NRF2/ KEAP1/P62/SQSTM1 Signaling Pathway in Different Glioma Subtypes: An In Silico Study |
| title_sort | comparative analysis of the mutation and expression profile of the cytoprotective nrf2 keap1 p62 sqstm1 signaling pathway in different glioma subtypes an in silico study |
| topic | nrf2/keap1/p62/sqstm1 signaling pathway glioma mutation gene expression oxidative stress |
| url |
http://namikkemalmedj.com/archives/archive-detail/article-preview/comparative-analysis-of-the-mutation-and-expressio/58941
|
| work_keys_str_mv | AT dilarafatmaakin comparativeanalysisofthemutationandexpressionprofileofthecytoprotectivenrf2keap1p62sqstm1signalingpathwayindifferentgliomasubtypesaninsilicostudy AT sedefhandeaktas comparativeanalysisofthemutationandexpressionprofileofthecytoprotectivenrf2keap1p62sqstm1signalingpathwayindifferentgliomasubtypesaninsilicostudy |