“Targeting MMP۷ in Rectal Cancer: Exploring the Therapeutic Potential ofBerberine through Bioinformatics and Molecular Docking Approaches”
سال انتشار: 1403
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 57
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شناسه ملی سند علمی:
ZISTCONF03_058
تاریخ نمایه سازی: 18 شهریور 1403
چکیده مقاله:
Rectal cancer, a significant subtype of colorectal cancer, poses a considerable health challenge due to itsaggressive nature and high mortality rate. This study aims to identify novel therapeutic targets in rectalcancer pathways and evaluate the potential of berberine, a natural isoquinoline alkaloid, as a treatmentoption. Using RNA sequencing data from The Cancer Genome Atlas (TCGA-COAD) project, weconducted a comprehensive bioinformatics analysis to identify differentially expressed genes (DEGs)between rectal tumor and normal tissues. Our analysis revealed ۱,۱۳۸ significant DEGs, comprising ۳۷۵upregulated and ۷۶۳ downregulated genes.Subsequently, we constructed and analyzed protein-proteininteraction (PPI) networks to identify hub genes crucial in rectal cancer development. From these, weselected five key proteins (COL۱A۱, MMP۱, MMP۳, MMP۷, CXCL۸) for molecular docking studies withberberine. The docking results demonstrated strong interactions between berberine and these proteins,with MMP۷ exhibiting the highest binding affinity (-۸.۶ kcal/mol).Further investigation into MMP۷'s rolein rectal cancer revealed its significance in extracellular matrix degradation, Wnt/β-catenin pathwayregulation, and tumor microenvironment modification. Although survival analysis for MMP۷ showed nosignificant difference between high and low expression groups, its importance in cancer progressioncannot be overlooked.Our study highlights berberine's potential in treating rectal cancer, particularlythrough its ability to inhibit MMP۷ activity and influence related signaling pathways. Additionally,berberine's anti-inflammatory and antioxidant properties may provide synergistic benefits in cancertreatment. These findings underscore the promise of berberine as a therapeutic agent for rectal cancer andemphasize the need for further research to fully elucidate its mechanisms of action and clinical efficacy.Inconclusion, this comprehensive analysis combining bioinformatics, molecular docking, and literaturereview provides valuable insights into the molecular underpinnings of rectal cancer and identifiesberberine as a promising compound for targeted therapy. Our results pave the way for future studiesaimed at developing novel treatment strategies for rectal cancer based on natural compounds likeberberine.
کلیدواژه ها:
نویسندگان
Omid Mohammadalizadeh
Department of Agronomy & Plant Breeding,Faculty of Sciences and Agricultural Engineering, TehranUniversity, Karaj, Iran
Java amini
Natural Products and Medicinal Plants Research Center, North Khorasan University of MedicalSciences, Bojnurd, Iran
Seyedamirreza sabzian
Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical Center, Columbus,Ohio, US
Ali AghadoukhtMamaghani
Brain Mind Institute, Life Sciences engineering School, EPFL, Lausanne, Switzerland