Transcriptome and Bisulfite sequencing of drug treated breast cancer cell lines

ST08 is a novel curcumin derivative that exhibited apoptotic and anti-migratory activity in MDA-MB-231, triple-negative breast cancer cells reported earlier. ST08 induced G2/M arrest in MCF7 but not in MDA-MB231 cells, whereas it induced apoptosis through the mitochondrial pathway in both cell lines. ST08 reduced tumor burden in vivo. ST08 potentiated the effect of cisplatin in vitro and in vivo in mouse EAC breast cancer model without any apparent toxicity. ST08 induced alterations in the gene expression were studied by parallel analysis of miRNA and mRNA. 136 and 74 differentially expressed miRNA regulated 349 and 114 mRNA in Luminal(MCF7) and triple negative(MDA-MB-231) cancer cells respectively. These signature miRNAs and mRNAs induced by ST08 segregated the luminal MCF7 and T47D (hormone positive) from MDA-MB231(hormone negative). Pathways altered in MCF, and T47D (hormone positive) cells were cell cycle regulation and ECM in MDA-MB231(hormone negative). We constructed unique miRNA-mRNA interaction networks specific to each cell line. One of the pathways regulated by miRNA was NF-KB common to MDA-MB-231 and MCF7. Targets of NF-KB like MMP1, PTX3 and MMP2 were downregulated in MDA-MB231 in response to ST08 treatment. PMA induced cell proliferation was abrogated by ST08 treatment validating regulation of NF-KB in breast cancer.