Effects of Berberine on Circular RNA Expression Profiles in Human Gastric Cancer Cells

  • Evid Based Complement Alternat Med. 2021 May 4:2021:6688629. doi: 10.1155/2021/6688629.
Meng Wang  1  2 ,  Letao Sun  3 ,  Li Wang  4 ,  Yongning Sun  1  4
Affiliations
  • 1. Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
  • 2. Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3. Gordon F. Derner School of Psychology, Adelphi University, New York 11530, USA.
  • 4. Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
PMID: 34055022 DOI: 10.1155/2021/6688629
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.

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