Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation
Abstract
:1. Introduction
2. Results
2.1. GPR55 Upregulation Occurs Predominantly during Activation of Immune Cells
2.2. Conditions Promoting LPI Accumulation Exist in Tumors and LPI Suppression Is Preferred during Differentiation
2.3. PACAP27 and PACAP38 Expression
3. Discussion
4. Materials and Methods
4.1. Software
4.2. Perturbations
4.3. Assessment of LPI Production Capacity
- The LPI-score was increased by one point (+1) whenever a gene positively affecting LPI level was upregulated or a gene negatively affecting LPI level was downregulated;
- Conversely, the LPI-score was decreased by on point (−1) whenever a gene positively affecting LPI level was downregulated or a gene negatively affecting LPI level was upregulated.
4.4. Assessment of PACAP27 and PACAP38 Production Capacity
- The PC-score was increased by one point (+1) whenever a convertase-coding gene (PCSK1, PCSK2, or PCSK4) was upregulated;
- The PC-score was decreased by one point (−1) whenever a convertase-coding gene (PCSK1, PCSK2, or PCSK4) was downregulated.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene Symbol | Full Name (Gene; Protein) | Effect on LPI | Mode of Action | Ref. |
---|---|---|---|---|
DDHD1 | DDHD domain containing 1; phospholipase DDHD1 | positive | involved in the formation of 2-arachidonoyl-LPI (endogenous agonist) | [15,16] |
PLA2G4A | phospholipase A2 group IVA; cytosolic phospholipase A2 | positive | involved in the formation of 2-stearotyl-LPI (endogenous agonist) | [15,18,19] |
ABCC1 (MRP1) | ATP binding cassette subfamily C member 1; multidrug resistance-associated protein 1 | positive | pumps LPI out of the cell enabling autocrine and paracrine activation of GPR55 | [18,19] |
ABHD6 | abhydrolase domain containing 6, acylglycerol lipase; monoacylglycerol lipase ABHD6 | negative | has lysophospholipase A activity; degrades LPI into GPI and a fatty acid, depleting agonist pool | [20] |
ENPP2 (ATX) | ectonucleotide pyrophosphatase/phosphodiesterase 2; autotaxin | negative | has lysophospholipase D activity; degrades LPI into LPA | [21,22] |
GDPD2 (GDE3) | glycerophosphodiester phosphodiesterase domain containing 2; glycerophosphoinositol inositolphosphodiesterase GDPD2, glycerophosphodiesterase 3 | negative | has lysophospholipase C activity; degrades LPI into 2-AG; generates CB2 agonist from LPI | [23] |
Gene Symbol | Full Name (Gene; Protein) | Effect on PACAP27/38 | Mode of Action | Ref. |
---|---|---|---|---|
ADCYAP1 (PACAP) | adenylate cyclase activating polypeptide 1; pituitary adenylate cyclase-activating polypeptide | positive | undergoes cleavage that generates PACAP-27 peptide (endogenous agonist of GPR55) | [10] |
PCSK1 (PC1) | proprotein convertase subtilisin/kexin type 1; neuroendocrine convertase 1; proprotein convertase 1 | positive | cleaves ADCYAP1-encoded polypeptide into shorter PACAP-27 | [27,28] |
PCSK2 (PC2) | proprotein convertase subtilisin/kexin type 2; neuroendocrine convertase 2; proprotein convertase 2 | positive | cleaves ADCYAP1-encoded polypeptide into shorter PACAP-27 | [27,28] |
PCSK4 (PC4) | proprotein convertase subtilisin/kexin type 4; proprotein convertase 4 | positive | cleaves ADCYAP1-encoded polypeptide into shorter PACAP-27 | [27,29] |
DPP4 (CD26, ADCP2) | dipeptidyl peptidase 4; cluster of differentiation 26, adenosine deaminase complexing protein 2 | negative | exopeptidase with a dipeptidyl peptidase activity; degrades PACAP-27 | [27] |
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Wnorowski, A.; Wójcik, J.; Maj, M. Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation. Int. J. Mol. Sci. 2021, 22, 13328. https://doi.org/10.3390/ijms222413328
Wnorowski A, Wójcik J, Maj M. Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation. International Journal of Molecular Sciences. 2021; 22(24):13328. https://doi.org/10.3390/ijms222413328
Chicago/Turabian StyleWnorowski, Artur, Jakub Wójcik, and Maciej Maj. 2021. "Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation" International Journal of Molecular Sciences 22, no. 24: 13328. https://doi.org/10.3390/ijms222413328