The UPR Transducer IRE1 Promotes Breast Cancer Malignancy by Degrading Tumor Suppressor microRNAs

To understand the mechanistic basis by which inositol-requiring enzyme 1 (IRE1) is involved in luminal breast cancer malignancy, we analyzed the transcriptomic signature that IRE1 regulates in breast cancer. We suppressed the activity of IRE1 RNase in luminal breast cancer SUM52 line by adenoviral-based over-expression of the IRE1 dominant-negative K599A or K907A, and then performed RNA-sequencing (RNA-seq) analysis with IRE1 dominant-negative and control SUM52 cells. Through the RNA-seq analysis, we identified 98 genes that were commonly upregulated (65 genes) or downregulated (33 genes) in K599A-expressing SUM52 (SUM52-K599A) or K907A-expressing SUM52 (SUM52-K907A) cells. Total RNAs from SUM52 cells transducted with the IRE1 dominant-negative K599A, K907A, or control adenovirus were harvested, frozen, and sent to the LC Sciences (Houston, TX, USA) for next-generation sequencing.