Abstract
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.
Highlights
Despite advancements in early diagnosis and therapeutics, such as surgery and chemoradiotherapy, the prognosis of gastric cancer (GC) remains relatively poor [1, 2]
Some studies reported that natural products such as nitidine chloride [12] and quercetin [13] exert anticancer effects or improve the prognosis of patients by influencing the expression of circular RNA (circRNA)
Berberine Decreased Cell Viability, Cell Proliferation, and Δψm and Induced Cell Apoptosis. e Cell Counting Kit-8 (CCK-8) analysis showed that AGS and HGC27 cell viability decreased in berberine concentration- and treatment time-dependent manners (0–80 μM and 0–72 h, respectively) (Figure 1(a))
Summary
Despite advancements in early diagnosis and therapeutics, such as surgery and chemoradiotherapy, the prognosis of gastric cancer (GC) remains relatively poor [1, 2]. Some studies reported that natural products such as nitidine chloride [12] and quercetin [13] exert anticancer effects or improve the prognosis of patients by influencing the expression of circRNAs. Several studies have demonstrated the important anticancer roles of berberine against malignant tumors, Evidence-Based Complementary and Alternative Medicine including GC [14]. RNA-seq was performed to identify circRNA expression profiles in AGS cells after berberine treatment. Enrichment analyses, based on the host genes of these 31 DE circRNAs and putative target mRNAs in the circRNAmiRNA-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. 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
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