PRJNA708316
RNA-seq data of Adenosine-treated Macrophages for Tumorigenic Effect
PurposeTumorigenic extracellular adenosine-targeted immunotherapy is one of the most promising candidates for advanced-stage cancers nonresponsive to currently approved PD1 signaling targeted immunotherapies. However, the mechanism of the tumorigenic effect of adenosine signaling axis for colorectal cancer is not fully understood. In this study, we aimed to reveal novel tumorigenic mechanisms of ATP adenosine signaling.MethodsTo investigate the effect of extracellular ATP and adenosine on tumor associated macrophages, we analyzed their transcriptional profiles via total RNA sequencing. Adenosine-treated macrophages were generated by deep sequencing, in triplicate, using Illumina NovaSeq 6000. The sequence reads that passed quality filters were analyzed at the transcript expression level with two methods, HISAT and StringTie. The significant genes were validated by qRT PCR and western blot.ResultsUsing an optimized data analysis workflow, we mapped about 70 million sequence reads per sample to the human genome hg38. Based on the results of RNA-seq, we found that extracellular adenosine signal increases PDL1 protein in macrophages through regulation of PDL1 protein stability via adenosine signal mediated decreased cyclin D1 and SPOP, resulting interference with formation of E3 ligase complex with Cullin 3 and Cullin 4B.ConclusionsOur study represents the detailed analysis of macrophage transcriptomes to understand the mechanism of the tumorigenic effect of adenosine signaling. This study strongly suggests potent advantages for lowering the expression level of PDL1 by ATP adenosine signaling inhibitors, which could contribute to their future clinical trials on advanced stage colorectal cancers.