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Transcriptome analysis of sinensetin-treated liver cancer cells guided by biological network analysis
Seong Min Kim1, Shailima Rampogu2, Preethi Vetrivel1
1Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam 52828, Republic of Korea.
Abstract:
Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of liver cancer globally, making the identification of biomarkers critically important. The aim of the present study was to identify the genes involved in the anticancer effects of flavonoid compounds so that they may be used as targets for cancer treatment. Sinensetin (SIN), an isolated polymethoxyflavone monomer compound, possesses broad antitumor activities in vitro. Therefore, the identification of a transcriptome profile on the condition of cells treated with SIN may aid to better understand the genes involved and its mechanism of action. Genomic profiling studies of cancer are increasing rapidly in order to provide gene expression data that can reveal prognostic biomarkers to combat liver cancer. In the present study, high-throughput RNA sequencing (RNA-seq) was performed to reveal differential gene expression patterns between SIN-treated and SIN-untreated human liver cancer HepG2 cells. A total of 43 genes were identified to be differentially expressed (39 downregulated and 4 upregulated in the SIN-treated group compared with the SIN-untreated group). An extensive network analysis for these 43 genes resulted in the identification of 10 upregulated highly interconnected hub genes that contributed to the progression of cancer. Functional enrichment analysis of these 10 hub genes revealed their involvement in the regulation of apoptotic processes, immune response and tumor necrosis factor production. Additionally, the mRNA expression levels of these 10 genes were evaluated using reverse transcription-quantitative PCR, and the results were consistent with the RNA-seq data. Overall, the results of the present study revealed differentially expressed genes involved in cancer after SIN treatment in HepG2 cells and may help to develop strategies targeting these genes for treating liver cancer.
Insights
Sinensetin (SIN) treatment altered gene expression in liver cancer cells, revealing potential therapeutic targets. This study identified key genes involved in cancer progression, offering new avenues for hepatocellular carcinoma treatment strategies.
Area of Science:
- * Oncology
- * Molecular Biology
- * Pharmacology
Background:
- * Hepatocellular carcinoma (HCC) is a prevalent global cancer requiring novel therapeutic targets.
- * Flavonoid compounds, like Sinensetin (SIN), exhibit promising in vitro antitumor activities.
- * Understanding gene expression changes induced by SIN is crucial for elucidating its anticancer mechanisms.
Purpose of the Study:
- * To identify genes modulated by Sinensetin (SIN) in human liver cancer HepG2 cells.
- * To explore the potential of these genes as therapeutic targets for hepatocellular carcinoma.
- * To investigate the molecular mechanisms underlying SIN's anticancer effects through transcriptome profiling.
Main Methods:
- * High-throughput RNA sequencing (RNA-seq) was employed to analyze gene expression profiles.
- * Differential gene expression analysis was performed between SIN-treated and untreated HepG2 cells.
- * Network analysis and functional enrichment were conducted on differentially expressed genes.
- * Reverse transcription-quantitative PCR (RT-qPCR) validated RNA-seq findings.
Main Results:
- * A total of 43 differentially expressed genes were identified (39 downregulated, 4 upregulated) in SIN-treated cells.
- * Network analysis highlighted 10 upregulated hub genes significantly associated with cancer progression.
- * Functional enrichment analysis indicated these hub genes are involved in apoptosis, immune response, and TNF production.
- * RT-qPCR confirmed the expression patterns observed in the RNA-seq data.
Conclusions:
- * Sinensetin (SIN) treatment significantly alters gene expression in hepatocellular carcinoma cells.
- * Identified hub genes represent potential therapeutic targets for liver cancer treatment.
- * The findings provide insights into the molecular mechanisms of SIN's antitumor activity.
