Metformin Affects the Transcriptomic Profile of Chicken Ovarian Cancer Cells

• Published in: Genes Vol. 13; no. 1; p. 30
• Main Authors: Gopalan, Lalitha, Sebastian, Aswathy, Praul, Craig A, Albert, Istvan, Ramachandran, Ramesh
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-12-2021; MDPI
• Subjects: Angiogenesis; Animals; Ascites; Ascites - drug therapy; ASCL1 protein; Cancer therapies; Cell culture; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Chickens; Diabetes; Digital cameras; DNA repair; Doublecortin protein; Down-Regulation - drug effects; Epidermal growth factor; Epithelial-Mesenchymal Transition - drug effects; Etiology; Extracellular matrix; Female; Invasiveness; Lipid metabolism; Malignancy; Matrilysin; Medical prognosis; Mesenchyme; Metformin; Metformin - pharmacology; NF-κB protein; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovary - drug effects; p53 Protein; Poultry; Signal Transduction - drug effects; Spheres; Stat3 protein; Stem cells; Transcriptome - drug effects; Transcriptomes; Transcriptomics; Up-Regulation - drug effects; Variance analysis; Vascular endothelial growth factor; Womens health; St Louis Missouri; Atlanta Georgia; United States > US; transcriptomics; metformin; animal models; ovarian cancer
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13010030

Ovarian cancer is the most lethal gynecological malignancy in women. Metformin intake is associated with a reduced incidence of ovarian cancer and increased overall survival rate. We determined the effect of metformin on sphere formation, extracellular matrix invasion, and transcriptome profile of ovarian cancer cells (COVCAR) isolated from ascites of chickens that naturally developed ovarian cancer. We found that metformin treatment significantly decreased sphere formation and invasiveness of COVCAR cells. RNA-Seq data analysis revealed 0, 4, 365 differentially expressed genes in cells treated with 0.5, 1, 2 mM metformin, respectively compared to controls. Transcriptomic and ingenuity pathway analysis (IPA) revealed significant downregulation of
,
,
,
,
and predicted inhibition of upstream regulators
,
,
that are involved in epithelial-mesenchymal transition, DNA repair, and lipid metabolism. The analysis revealed significant upregulation of
,
,
and predicted activation of upstream regulators VEGF and E2F1 that are associated with angiogenesis and cell cycle. Causal network analysis revealed novel pathways suggesting predicted inhibition of ovarian cancer through master regulator
and dataset genes
,
,
, and
. In summary, advanced pathway analysis in IPA revealed novel target genes, upstream regulators, and pathways affected by metformin treatment of COVCAR cells.