Effect of CRY2 stabilizer and proteasome inhibitor on the transcription of MDA-MB-231 cells [RNA-seq]

In this study we tested if the transcriptional activity of circadian transcription factors, BMAL1 and CLOCK, can be repressed by small molecules in triple negative breast cancer cells. We validated that CRY inhibitors and proteasome inhibitors synergize and can recapitulate the phenotype of genetic knockdown of BMAL1 and CLOCK. To investigate the potential mechanism of the effect of this drug combination, we performed RNA sequencing analysis on cells treated with either single drug or drug combination at different time points. We tested the effect of two kinds of proteasome inhibitors, either as a single agent or in combination with CRY stabilizer SHP1705, on the transcription of triple negative breast cancer cell line MDA-MB-231. Three independent experiments are performed. Each experiment includes DMSO-treated (control), SHP1705-treated, proteasome inhibitor-treated, and the combination of two drugs-treated. For MG132 combination experiment, the cells were treated for eight hours. For carfilzomib (CFZ) combination experiment, the cells were treated for 8 or 24 hours.