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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156332 | GEO | 2021/01/15

REPOSITORIES: GEO

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IRE1 modulates expression of a set of tumor suppressor miRNAs in luminal breast cancer cells.

Project description:To explore the regulatory mechanism by which inositol-requiring enzyme 1 (IRE1) regulates oncogenic factors, particularly RAB3B, in luminal breast cancer cells, we blocked IRE1 activity in breast cancer cell lines by using the IRE1 inhibitor 4μ8C or expressing IRE1 dominant-negative for miRNA microarray analysis. SUM52 and SUM225 lines with high-level IRE1 expression were treated with 4μ8C for 2 days. The IRE1 kinase dominant-negative mutant K599A or K907A was also used to suppress IRE1 kinase or RNase activity in SUM52 cells. The miRNA microarray analysis revealed a landscape change in miRNA expression profiling in IRE1-inhibited luminal breast cancer cells. Using a criterion of p < 0.05 in miRNA analysis, we identified 41 miRNAs in both SUM52 and SUM225 cells that were altered after inhibiting IRE1 activity. Additionally, we exogenously overexpressed wild-type IRE1 in human nontumorigenic mammary epithelial MCF10A cells and then performed miRNA array assays. When we combined miRNA data from both IRE1 inhibition models in breast cancer cells and exogenous overexpression of IRE1 in MCF10A cells (p<0.05), we identified 5 miRNAs (3607-3p, 374a-5p, 4764-3p, 516a-3p, and 6073) that were upregulated in IRE1-inhibited breast cancer cells and downregulated in MCF10A-IRE1 cells.

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

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

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

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IRE1-dependent transcriptome remodelling upon ER stress in human glioma cells

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Gene profiling: U87 IRE1 dominant negative cells vs. U87ctrl cells in culture

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MDA-MB-231 gene expression upon IRE1 RNase inhibition with MKC-8866

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IRE1 modulates expression of a set of tumor suppressor miRNAs in luminal breast cancer cells.

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