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Series GSE147264 Query DataSets for GSE147264
Status Public on Dec 21, 2022
Title COX-2/PGE2 upregulation contributes to the chromosome 17p-deleted lymphoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Chromosome 17p deletions are one of the most frequent chromosomal alterations in human cancers and also lymphoma. Although it has been assumed to be equal to p53 loss for a long time, there are emerging evidence suggesting that there would be additional p53–independent mechanisms. Our previous work identified ALOX15B, an arachidonate lipoxygenase, as a 17p tumor suppressor in lymphoma. Interestingly, five of the six ALOX genes locate on this region and frequently co-deleted with TP53. Among them, ALOX15B, ALOX12B and ALOXE3 are adjacent to one another and proximal to the centromere relative to TP53, while ALOX12 and ALOX15 are distal to the centromere relative to TP53. Herein, we show that each of the five 17p ALOX genes repress Myc-driven lymphomagenesis in mice. Mechanistically, deficiency of the ALOX arachidonate metabolism pathway activates the paralleling COX-PGE2 pathway, resulting in increasing PTGS2 expression and PGE2 level. PGE2 prevents apoptosis of pre-B cells and Ptgs2 knockdown extends the latency of Myc;shAlox15b lymphoma in vivo. Further, shAlox15b lymphoma cells are more sensitive to COX-2 inhibitor celecoxib than control lymphoma cells. Importantly, the ALOX-COX metabolism unbalance is also observed in human cancers with del(17p). Taken together, our studies reveal the tumor suppression functions of all of the five ALOX genes on chromosome 17p in lymphoma and an unprecedented arachidonate metabolism unbalance between the ALOX and COX pathways underlying human cancers with 17p deletions.
 
Overall design Bulk RNA sequencing in Alox15b and Alox12b knock down Pre-B cells.
Web link https://pubmed.ncbi.nlm.nih.gov/36750552/
 
Contributor(s) Pan X, Chen X, Xu Z, Qi L, Liu P, Chen M, Zhang Q, Hang X, Tang M, Wen D, Lowe SW, Niu T, Chen C, Liu Y
Citation(s) 36750552
Submission date Mar 20, 2020
Last update date Mar 23, 2023
Contact name Xaingyu Pan
E-mail(s) pangxueyu233@outlook.com
Organization name Sichuan University
Department State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.
Lab Chen & Liu Lab
Street address No.17 Renming road section3
City Chengdu, Cihna
State/province Sichuan
ZIP/Postal code 610041
Country China
 
Platforms (1)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (10)
GSM4422868 shAlox12b.728_1bulkRNAseq
GSM4422869 shAlox12b.728_2bulkRNAseq
GSM4422870 shAlox12b.728_3bulkRNAseq
Relations
BioProject PRJNA613637
SRA SRP253460

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Supplementary file Size Download File type/resource
GSE147264_Multiple_ALOX_RNAseq_TPM_anno_.xlsx 10.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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