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Effect of persistent ER stress on gene expression of pancreatic ductal adenocarcinoma cell AsPC1

ABSTRACT: To investigate the changes of gene expression in pancreatic ductal adenocarcinoma cells under persistent endoplasmic reticulum stress, we treated AsPC-1 cells with 30 nM thapsigargin (Tg) for more than 14 days (designated as AsPC-1-Tg). To investigate whether the effects of persistent ER stress on gene expression is permanent or reversible, we cultured AsPC-1-Tg cells in a medium without Tg (designated as AsPC-1-Tg-Re) for 4 days. In this study, we then performed gene expression profiling analysis using data obtained from high-throughput RNA-seq (include mRNA, lncRNA, circRNA and miRNA) of AsPC-1 (WT), AsPC-1-Tg (TG) and AsPC-1-Tg-Re (RE) cells. Three biological replicates of each sample were used for RNA-seq.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229941 | GEO | 2023/08/09

REPOSITORIES: GEO

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Project description:INS1-EGFP-L10a stable cell lines were induced with Doxycycline (Dox) for 24 hours, then either untreated or treated for 30 minutes with 1uM Thapsigargin to induce ER stress. Total RNA was purified with Trizol, and RIP RNA samples were extracted by immunoaffinity purification using an EGFP antibody We aimed to determine which genes are enriched under ER stress at the polyribosomal level. To do this we compared expression profiles of Total RNA with and without ER stress, and Immunoaffinity purified RNA (RIP) with and without ER stress. Microarray results of INS-1 EGFP-L10a cells either untreated or treated with 1uM Thapsigargin (Tg) in triplicate. Both Total RNA and RNA isolated from ribosomal Immunoprecipitation (RIP) When unfolded proteins accumulate to irremediably high levels within the endoplasmic reticulum (ER), intracellular signaling pathways called the unfolded protein response (UPR) become hyperactivated to cause programmed cell death. We discovered that thioredoxin-interacting protein (TXNIP) is a critical node in this M-bM-^@M-^\Terminal UPRM-bM-^@M-^]. TXNIP becomes rapidly induced by hyperactivated IRE1a, an ER bifunctional kinase/endoribonuclease (RNase). IRE1a controls TXNIP mRNA stability by reducing levels of a TXNIP destabilizing micro-RNA, miR-17. In turn, elevated TXNIP protein activates the NLRP3 inflammasome, causing Caspase-1 cleavage and interleukin 1b (IL-1b) secretion. Txnip gene deletion reduces pancreatic b-cell death during ER stress, and suppresses diabetes caused by proinsulin misfolding in the Akita mouse. Finally, small molecule IRE1a RNase inhibitors suppress TXNIP production to block IL-1b secretion. In summary, the IRE1a-TXNIP pathway is used in the terminal UPR to promote sterile inflammation and programmed cell death, and may be targeted to develop new treatments for degenerative diseases driven by ER stress. There are 12 samples total all in INS-1 EGFP L10a cells- 3 untreated total RNA (reference sample), 3 treated with 1uM Tg 30 min total RNA, 3 untreated RIP RNA (reference sample), 3 treated with 1uM for 30 min RIP RNA

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Effect of persistent ER stress on gene expression of pancreatic ductal adenocarcinoma cell AsPC1

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