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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Functional Cross-Talking between Differentially Expressed and Alternatively Spliced Genes in Human Liver Cancer Cells
Zhen Sheng1, Yi Sun1, Ruixin Zhu1
1School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
Abstract:
Berberine has been identified with anti-proliferative effects on various cancer cells. Many researchers have been trying to elucidate the anti-cancer mechanisms of berberine based on differentially expressed genes. However, differentially alternative splicing genes induced by berberine might also contribute to its pharmacological actions and have not been reported yet. Moreover, the potential functional cross-talking between the two sets of genes deserves further exploration. In this study, RNA-seq technology was used to detect the differentially expressed genes and differentially alternative spliced genes in BEL-7402 cancer cells induced by berberine. Functional enrichment analysis indicated that these genes were mainly enriched in the p53 and cell cycle signalling pathway. In addition, it was statistically proven that the two sets of genes were locally co-enriched along chromosomes, closely connected to each other based on protein-protein interaction and functionally similar on Gene Ontology tree. These results suggested that the two sets of genes regulated by berberine might be functionally cross-talked and jointly contribute to its cell cycle arresting effect. It has provided new clues for further researches on the pharmacological mechanisms of berberine as well as the other botanical drugs.
Insights
Berberine exhibits anti-cancer properties by influencing both gene expression and alternative splicing. These gene sets interact functionally, suggesting a combined role in cell cycle arrest and berberine
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- Berberine demonstrates anti-proliferative effects on cancer cells.
- Existing research focuses on differentially expressed genes, neglecting alternative splicing.
- The functional interplay between differentially expressed and spliced genes remains unexplored.
Purpose of the Study:
- To investigate berberine-induced differentially expressed and alternative spliced genes in BEL-7402 cancer cells.
- To explore the functional crosstalk between these two gene sets.
- To elucidate novel anti-cancer mechanisms of berberine.
Main Methods:
- RNA-sequencing (RNA-seq) to identify differentially expressed and alternative spliced genes.
- Functional enrichment analysis (e.g., Gene Ontology, KEGG pathways).
- Protein-protein interaction network analysis.
Main Results:
- Berberine induced significant changes in both gene expression and alternative splicing in BEL-7402 cells.
- Enriched pathways included p53 signaling and cell cycle regulation.
- Genes showed chromosomal co-enrichment, protein-protein interaction, and functional similarity.
Conclusions:
- Differentially expressed and alternative spliced genes regulated by berberine exhibit functional crosstalk.
- These gene sets jointly contribute to berberine's cell cycle arresting effects.
- Findings offer new insights into berberine's pharmacological mechanisms and botanical drug research.
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