Identification of the effect of cisplatin on the transcriptome of human hepatocellular carcinoma cell lines

doi:10.16352/j.issn.1001-6325.2024.03.0352

Abstract

Abstract: Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with different concentrations of cisplatin (CDDP). Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L. After 12 hours, cell viability, immunofluorescence and RNA-sequencing(RNA-seq) were performed. Differential gene expression analysis (DEG), KEGG pathway analysis, and protein-protein interaction network analysis were conducted. Results Cisplatin decreased cell viability and increased DNA damage in HepG2,Huh7 cells. Among the genes regulated after cisplatin treatment at different concentrations, 59 genes were commonly up-regulated in both HepG2 and Huh7 cells, while 81 genes were commonly down-regulated. The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway, Ras signaling pathway, signaling pathways regulating pluripotency of stem cells, axon guidance, and cell adhesion-related pathways. Survival analysis of key nodes in the protein-protein interaction network of commonly upregulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene, AP-1 transcription factor subunit (JUN) and prolonged patient survival and a significant correlation between low expression of growth arrest and DNA damage inducible alpha (GADD45A) and prolonged patient survival. Conclusions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment. Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance. This conclusion provides some important prognostic indicators for clinical treatment.

Key words: liver cancer, transcriptome sequencing, cisplatin, gene transcription

CLC Number:

GUO Xin, JI Mengdie, WANG Qi, LI Xueyuan, CHEN Yang. Identification of the effect of cisplatin on the transcriptome of human hepatocellular carcinoma cell lines[J]. Basic & Clinical Medicine, 2024, 44(3): 352-360.

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