Bioinformatics analysis of VCAN as a key target in colorectal cancer cisplatin resistance
10.19405/j.cnki.issn1000-1492.2025.04.006
- VernacularTitle:基于生物信息学分析VCAN作为结直肠癌顺铂耐药关键靶点研究
- Author:
Jingxian Li
1
;
Huiguang Chen
2
;
Jianze Wu
1
;
Dequan Wang
1
;
Zhifen Chen
3
;
Qingming Wu
4
Author Information
1. Institute of Infection ，Immunology and Tumor Microenvironment ，Wuhan University of Science and Technology，Hubei Prorince Key Laboratory of Occupational Hazard Identification and Control，Wuhan 430081
2. Institute of Infection ，Immunology and Tumor Microenvironment ，Wuhan University of Science and Technology，Hubei Prorince Key Laboratory of Occupational Hazard Identification and Control，Wuhan 430081; Center of Basic Medical Research，Institute of Medical Innovation and Research，Peking University Third Hospital，Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology ( BLGO) ， Beijing 100191
3. Dept of Gastroenterology，Zhongnan Hospital of Wuhan University，Hubei Clinical Center and Key Laboratory for Intestinal and Colorectal Diseases，Wuhan 430071
4. Institute of Infection ，Immunology and Tumor Microenvironment ，Wuhan University of Science and Technology，Hubei Prorince Key Laboratory of Occupational Hazard Identification and Control，Wuhan 430081; Dept of Gastroenterology， Tianyou Hospital，Wuhan University of Science and Technology，Wuhan 430064
- Publication Type:Journal Article
- Keywords:
VCAN;
cisplatin;
bioinformatics;
transcriptomic sequencing;
AKT-mTOR signaling pathway;
chemo- therapy resistance
- From:
Acta Universitatis Medicinalis Anhui
2025;60(4):624-633
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment.
Methods:Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes.
Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway.
Conclusion:Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.
- Full text:2026012609371196139基于生物信息学分析VCAN...直肠癌顺铂耐药关键靶点研究_李静娴.pdf
