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Published on: August 25, 2020
RNA-Seq analysis of interferon inducible p204-mediated network in anti-tumor immunity
Jinlong Jian1,2, Wei Wei1, Guowei Yin1
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China.
Abstract:
p204, a murine member of the interferon-inducible p200 protein family, and its human analogue, IFI16, have been shown to function as tumor suppressors in vitro, but the molecular events involved, in particular in vivo, remain unclear. Herein we induced the Lewis Lung carcinoma (LLC) murine model of human lung cancer in p204 null mice (KO) and their control littermates (WT). We compared the transcriptome in spleen from WT and p204 KO mice using a high-throughput RNA-sequencing array. A total 30.02 Gb of clean data were obtained, and overall Q30% was greater than 90.54%. More than 75% of clean data from 12 transcriptome samples were mapped to exons. The results showed that only 11 genes exhibited altered expression in untreated p204 KO mice relative to untreated WT mice, while 393 altered genes were identified in tumor-bearing p204 KO mice when compared with tumor-bearing WT mice. Further differentially expressed gene cluster and gene ontology consortium classification revealed that numerous cytokines and their receptors, chemoattractant molecules, and adhesion molecules were significantly induced in p204 KO mice. This study provides novel insights to the p204 network in anti-tumor immune response and also presents a foundation for future work concerning p204-mediated gene expressions and pathways.
Insights
The p204 protein is crucial for anti-tumor immunity. Its absence in mice significantly alters immune gene expression, particularly in response to lung cancer, revealing its role in the immune network.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- The tumor suppressor role of p204 (murine) and IFI16 (human) is established in vitro, but in vivo mechanisms are unclear.
- Interferon-inducible p200 family proteins are implicated in cellular processes, including tumor suppression.
Purpose of the Study:
- To investigate the in vivo role of p204 in anti-tumor immune response using a Lewis Lung carcinoma (LLC) model.
- To compare the transcriptome of p204 null (KO) and wild-type (WT) mice to identify molecular events associated with p204 deficiency.
Main Methods:
- Lewis Lung carcinoma (LLC) model induced in p204 KO and WT mice.
- High-throughput RNA-sequencing of spleen transcriptome.
- Differential gene expression analysis and Gene Ontology (GO) classification.
Main Results:
- Minimal gene expression changes in untreated p204 KO vs. WT mice (11 genes).
- Significant alterations in gene expression in tumor-bearing p204 KO vs. WT mice (393 genes).
- Upregulation of cytokines, cytokine receptors, chemoattractants, and adhesion molecules in p204 KO mice with tumors.
Conclusions:
- p204 plays a significant role in regulating the anti-tumor immune response in vivo.
- Loss of p204 impacts immune cell signaling pathways, including those involving cytokines and cell adhesion.
- This study provides a foundation for understanding p204-mediated gene expression in cancer immunity.
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