Targeting PERK and GRP78 in colorectal cancer: Genetic insights and novel therapeutic approaches
Rattachement africain : ir, ca, pl, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Colorectal cancer (CRC) ranks among the leading causes of cancer-related deaths worldwide. Enhancing CRC diagnosis and prognosis requires the development of improved biomarkers and therapeutic targets. Emerging evidence suggests that the unfolded protein response (UPR) plays a pivotal role in CRC progression, presenting new opportunities for diagnosis, treatment, and prevention. This study hypothesizes that genetic variants in endoplasmic reticulum (ER) stress response genes influence CRC susceptibility. We examined the frequencies of SNPs in PERK (rs13045) and GRP78/BiP (rs430397) within a South Iranian cohort. We mapped the cellular and molecular features of PERK and GRP78 genes in colorectal cancer, observing their differential expressions in tumor and metastatic tissues. We constructed co-expression and protein-protein interaction networks and performed gene set enrichment analysis, highlighting autophagy as a significant pathway through KEGG. Furthermore, the study included 64 CRC patients and 60 control subjects. DNA extraction and genotyping were conducted using high-resolution melting (HRM) analysis. Significant differences in PERK and GRP78 expressions were observed between CRC tissues and controls. Variations in PERK and GRP78 genotypes were significantly correlated with CRC risk. Utilizing a Multi-Target Directed Ligands approach, a dual PERK/GRP78 inhibitor was designed and subjected to molecular modeling studies. Docking experiments indicated high-affinity binding between the proposed inhibitor and both genes, PERK and GRP78, suggesting a novel therapy for CRC. These findings highlight the importance of understanding genetic backgrounds in different populations to assess CRC risk. Polymorphisms in UPR signaling pathway elements may serve as potential markers for predicting CRC susceptibility, paving the way for personalized therapeutic strategies.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Targeting PERK and GRP78 in colorectal cancer: Genetic insights and novel therapeutic approaches
- Date Crossref
- 01/11/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Yasuj University of Medical Sciences Cellular and Molecular Research Center pays non établi dans la noticeUniversité ou école supérieure
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Shiraz University of Medical Sciences Hematology Research Center pays non établi dans la noticeUniversité ou école supérieure
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Research Institute for Gastroenterology and Liver Diseases pays non établi dans la noticeStructure de recherche
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Shahid Beheshti University of Medical Sciences Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center pays non établi dans la noticeUniversité ou école supérieure
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University of Guelph pays non établi dans la noticeUniversité ou école supérieure
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Tehran University of Medical Sciences Oncology and Stem Cell Transplantation Research Center pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Warsaw pays non établi dans la noticeUniversité ou école supérieure
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California State University Department of Chemistry and Biochemistry pays non établi dans la noticeUniversité ou école supérieure
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Silesian University of Technology Biotechnology Center pays non établi dans la noticeUniversité ou école supérieure
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CancerCare Manitoba pays non établi dans la noticeÉtablissement de santé
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Research Institute in Oncology and Hematology pays non établi dans la noticeStructure de recherche
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University of Manitoba pays non établi dans la noticeUniversité ou école supérieure
Cellular and Molecular Research Center — Yasuj University of Medical Sciences, Hematology Research Center — Shiraz University of Medical Sciences et Research Institute for Gastroenterology and Liver Diseases, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.