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Effects of Berberine on Circular RNA Expression Profiles in Human Gastric Cancer Cells
Background:
Berberine has been demonstrated to have anticancer effects against gastric cancer (GC), but the mechanism of these actions is unclear.
Objectives:
To explore the impact of berberine on circular RNA (circRNA) expression profiles in GC and investigate the potential molecular mechanisms associated with circRNAs in GC.
Methods:
AGS and HGC27 GC cells were treated with various concentrations of berberine. Cell viability was measured using a Cell Counting Kit-8 assay. Cell proliferation was measured using a cell colony formation assay. Cell apoptosis was measured using flow cytometry. The mitochondrial membrane potential (Δψm) was determined using a JC-1 probe. RNA-seq was performed to identify circRNA expression profiles in AGS cells after berberine treatment. Selected differentially expressed (DE) circRNAs were verified using RT-qPCR. Bioinformatics analysis was performed to predict target miRNAs and mRNAs and construct a circRNA-miRNA-mRNA network. Pathway and process enrichment analyses were performed to explore the potential biological roles of DE circRNAs.
Results:
Berberine decreased GC cell viability, cell proliferation, and Δψm and induced cell apoptosis. Thirty-one DE circRNAs were identified in the berberine-treated group compared to the control group, among which circRNA2499, hsa_circ_0003423, and hsa_circ_0006702 were validated using RT-qPCR. Enrichment analyses, based on the host genes of these 31 DE circRNAs and putative target mRNAs in the circRNA-miRNA-mRNA network of the validated circRNAs, indicated that berberine exerts anti-GC effects in multiple pathways including the Notch, MAPK, and NF-κB signaling pathways via specific circRNAs.
Conclusion:
This study elucidated the expression profile of circRNAs in human GC cells after berberine treatment. Our results demonstrate that berberine has the potential to influence cancer-related pathways by regulating circRNA expression and their corresponding target genes in GC cells.
Insights
Berberine, a natural compound, combats gastric cancer (GC) by altering circular RNA (circRNA) expression. This study reveals berberine
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Berberine exhibits anticancer properties against gastric cancer (GC).
- The precise molecular mechanisms underlying berberine's anti-GC effects remain largely unexplored.
- Circular RNAs (circRNAs) are implicated in cancer development and progression.
Purpose of the Study:
- To investigate the impact of berberine on circRNA expression profiles in GC.
- To elucidate the molecular mechanisms through which circRNAs mediate berberine's anti-GC actions.
- To identify specific circRNAs and associated pathways affected by berberine treatment in GC cells.
Main Methods:
- Gastric cancer cell lines (AGS, HGC27) were treated with berberine.
- Cell viability, proliferation, apoptosis, and mitochondrial membrane potential were assessed.
- RNA sequencing (RNA-seq) identified differentially expressed circRNAs (DEcircRNAs).
- RT-qPCR validated key DEcircRNAs.
- Bioinformatics analyses constructed circRNA-miRNA-mRNA networks and identified enriched pathways.
Main Results:
- Berberine reduced GC cell viability and proliferation while inducing apoptosis and decreasing mitochondrial membrane potential.
- Thirty-one DEcircRNAs were identified, with circRNA2499, hsa_circ_0003423, and hsa_circ_0006702 validated.
- Enrichment analyses linked berberine's anti-GC effects to the Notch, MAPK, and NF-κB signaling pathways via specific circRNAs.
Conclusions:
- Berberine modulates circRNA expression profiles in human GC cells.
- Berberine influences key cancer-related pathways through the regulation of circRNAs and their target genes.
- This study provides insights into the molecular mechanisms of berberine's anti-GC effects, highlighting the role of circRNAs.
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