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Updated: Jun 15, 2025
Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Identifying key genes against rutin on human colorectal cancer cells via ROS pathway by integrated bioinformatic
1Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Abstract:
Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.
Insights
Rutin, a fruit polyphenol, shows promise in treating colorectal cancer (CRC) by targeting key genes involved in cell growth and death. This study combined bioinformatics and experiments to validate its therapeutic potential.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Colorectal cancer (CRC) is a major global health concern with varying incidence rates.
- Rutin, a naturally occurring polyphenol found in fruits, is being investigated for its potential anti-cancer properties.
Purpose of the Study:
- To identify molecular targets and pathways affected by rutin in colorectal cancer.
- To integrate bioinformatic analysis with experimental validation for a comprehensive understanding of rutin's efficacy.
Main Methods:
- Gene Set Enrichment Analysis (GSEA) and network analysis (STITCH, Cytoscape) to identify key genes and pathways.
- Utilized databases like GEO2R, CTD, Gene Cards, UALCAN, and GEPIA for target identification and validation.
- Experimental validation included MTT assays, flow cytometry, and RT-PCR on HT-29 colorectal cancer cells.
Main Results:
- Identified 16 potential targets and six highly upregulated genes (TP53, PCNA, CDK4, CCNEB1, CDKN1A, LDHA) in the rutin network.
- Rutin demonstrated antioxidant properties and influenced metabolic, ROS, HIF1a, and mTOR signaling pathways.
- Rutin inhibited HT-29 cell growth, induced G1 phase arrest, promoted cell death, and reduced target gene expression.
Conclusions:
- Rutin exhibits significant therapeutic potential for colorectal cancer.
- The study provides a holistic view of rutin's efficacy through integrated computational and experimental approaches.
- Rutin represents a promising natural compound for CRC treatment development.
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