Identifying key genes against rutin on human colorectal cancer cells via ROS pathway by integrated bioinformatic analysis and experimental validation

芦丁 结直肠癌 钥匙(锁) 基因 计算生物学 癌症研究 癌症 化学 生物 细胞生物学 生物化学 遗传学 抗氧化剂 生态学
作者
Mansour K. Gatasheh
出处
期刊:Computational Biology and Chemistry [Elsevier]
卷期号:112: 108178-108178
标识
DOI:10.1016/j.compbiolchem.2024.108178
摘要

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.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
huang发布了新的文献求助30
刚刚
1秒前
2秒前
2秒前
星你完成签到,获得积分10
4秒前
4秒前
玻璃外的世界完成签到,获得积分10
4秒前
摆烂小子发布了新的文献求助20
5秒前
kingwill应助cong1216采纳,获得20
5秒前
科研通AI5应助机灵海云采纳,获得10
5秒前
6秒前
大白发布了新的文献求助10
7秒前
8秒前
海小贝发布了新的文献求助10
8秒前
犹豫的初丹完成签到,获得积分10
9秒前
暮光之城发布了新的文献求助10
9秒前
10秒前
10秒前
只A不B应助swordlee采纳,获得30
11秒前
橘温茶暖完成签到 ,获得积分10
11秒前
复杂元瑶发布了新的文献求助10
11秒前
xiaowan发布了新的文献求助10
12秒前
干净的凡桃完成签到,获得积分10
12秒前
12秒前
12秒前
科研通AI5应助tian采纳,获得10
13秒前
13秒前
13秒前
湘江雨完成签到,获得积分10
13秒前
SciGPT应助yongziwu采纳,获得10
13秒前
丘比特应助健忘的妙柏采纳,获得10
14秒前
14秒前
摆烂小子完成签到,获得积分10
15秒前
yangting发布了新的文献求助10
15秒前
风中的文龙完成签到,获得积分10
16秒前
美丽访云发布了新的文献求助20
16秒前
16秒前
大壮完成签到,获得积分10
17秒前
code12ab完成签到,获得积分20
17秒前
18秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Mechanistic Modeling of Gas-Liquid Two-Phase Flow in Pipes 2500
Kelsen’s Legacy: Legal Normativity, International Law and Democracy 1000
Handbook on Inequality and Social Capital 800
Conference Record, IAS Annual Meeting 1977 610
Interest Rate Modeling. Volume 3: Products and Risk Management 600
Interest Rate Modeling. Volume 2: Term Structure Models 600
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3546689
求助须知:如何正确求助?哪些是违规求助? 3123769
关于积分的说明 9356697
捐赠科研通 2822394
什么是DOI,文献DOI怎么找? 1551413
邀请新用户注册赠送积分活动 723398
科研通“疑难数据库(出版商)”最低求助积分说明 713736