Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1

The aim of this study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. We performed RNA sequencing (RNA-Seq) and obtained a list of differentially expressed genes (DEGs) in Bcl2l10-suppressed SKOV3 and A2780 cells. RNA-Seq data showed that DEGs after Bcl2l10 knockdown are involved in transcriptional regulation and energy metabolism in ovarian cancer cells. The RNA-Seq data were validated by quantitative real-time PCR (qRT-PCR) and western blot analysis, and the levels of metabolites after Bcl2l10 knockdown were measured by ELISA. KEGG enrichment analysis showed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10 knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from the RNA-Seq and validated by qRT-PCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, are potential downstream targets of Bcl2l10. We further found that Bcl2l10 knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. Overall design: Identification of differentially expressed genes after Bcl2l10 knockdown in SKOV3 and A2780 cells