Supplementary Figures S1-6. from BRCA1 Deficiency Upregulates NNMT, Which Reprograms Metabolism and Sensitizes Ovarian Cancer Cells to Mitochondrial Metabolic Targeting Agents
Year: 2023
Type: supplementary-materials
Abstract: Supplementary Figures S1-6. Supplementary Fig. S1 shows that CDK12 depletion alters ATP and ADP levels without affecting glycolysis in cell lines. Supplementary Fig. S2 shows that BRCA1 depletion does not affect glycolysis, that CDK12 and BRCA1 depletion reduce ATP levels in ex vivo HGSOC PDX cultures, that transient BRCA1 expression increase OCR in BRCA1-deficient cells, that CDK12 and BRCA1 depletion do not affect mitochondrial DNA levels, and levels of BRCA1 and CDK12 mRNA expression in cells transfected with CDK12 siRNAs and BRCA1 expression plasmid. Supplementary Fig. S3 shows BRCA2 and RAD51 depletion do not affect OCR but do sensitize to olaparib. Supplementary Fig. S4 shows a map of known BRCA1 transcripts, the exons that are targeted by the BRCA1 siRNAs used in this study, primers used to assess expression of alternative BRCA1 transcripts, NNMT mRNA expression in cells transfected with BRCA1 siRNAs, and binding of BRCA1 to the NNMT promoter using ChIP. Supplementary S5 shows that BRCA2 and RAD51 depletion do not sensitize to VLX600 but do sensitize to olaparib. Supplementary Fig. S6 shows that CDK12 and BRCA1 depletion does not further suppress ATP levels in NNMT-overexpressing cells.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362423008