RAGE Inhibitor TTP488 (Azeliragon) Reduces Metastasis in Triple-Negative Breast Cancer
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ABSTRACT:
PROVIDER: PRJNA884681 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21726053_1.fastq.gz | Fastqsanger.gz | |||
| SRR21726053_2.fastq.gz | Fastqsanger.gz | |||
| SRR21726054_1.fastq.gz | Fastqsanger.gz | |||
| SRR21726054_2.fastq.gz | Fastqsanger.gz | |||
| SRR21726055_1.fastq.gz | Fastqsanger.gz |
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Project description:Cell surface heparan sulfate (HS) plays an essential role in RAGE signaling by inducing RAGE oligomerization. To understand the physiological significance of HS-induced RAGE oligomerization in vivo, we generated RAGE knock-in mice (RageAHA/AHA) by introducing point mutations to specifically disrupt HS–RAGE interaction. The RAGE variant expressed by RageAHA/AHA mice demonstrated normal ligand-binding but greatly impaired capacity of HS-binding and oligomerization. To grasp the full scale of the alteration in gene expression caused by knocking out Rage, we performed a RNAseq analysis of mature neutrophils and lung from WT, RageAHA/AHA and Rage-/- mice. The overall number of differently regulated genes (DEGs) in Rage-/- neutrophils were almost 2.5 times higher than in RageAHA/AHA neutrophils (603 vs. 247). In contrast, the number of DEGs were much less in lungs compared to neutrophils in both strains (202 DEGs in Rage-/- lungs and merely 31 DEGs in RageAHA/AHA lungs), however the difference between the two genotypes was even more dramatic in lungs (7-fold) than we observed in neutrophils (2.5-fold). By comparing transcriptomes of neutrophils and lung tissues from RageAHA/AHA and Rage-/- mice, we present clear evidence that complete deficiency of RAGE had much broader impact on global gene expression compared to point mutations of RAGE.
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