Myeloid Zfhx3 Deficiency Protects Against Hypercapnia-induced Suppression of Host Defense Against Influenza A Virus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA762340 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15844682.fastq.gz | Fastqsanger.gz | |||
| SRR15844683.fastq.gz | Fastqsanger.gz | |||
| SRR15844684.fastq.gz | Fastqsanger.gz | |||
| SRR15844685.fastq.gz | Fastqsanger.gz | |||
| SRR15844686.fastq.gz | Fastqsanger.gz |
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Project description:Zfhx3, human ortholog of the Drosophila Zfh2 and first known mediator of hypercapnic immune suppression in vivo, is expressed in human and mouse MØs and its myeloid deletion reversed the effects of hypercapnia in gene expression in murine alveolar macrophages and protects against influenza A virus proliferation, lung injury and mortality increased by hypercapnia in infected mice.
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Project description:Myeloid Zfhx3 Deficiency Protects Against Influenza A Virus-induced Lung Injury and Mortality Increased by Hypercapnia
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Project description:Zinc-finger homeobox 3 (ZFHX3, also known as ATBF1) suppresses prostatic tumorigenesis. ZFHX3 is frequently found to have numerous deletions in human prostate cancer (PCa). However, the underlying molecular function of ZFHX3 during prostatic tumorigenesis is not well understood. N6-methyladenosine (m6A) modification in RNA plays a critical role in the development of cancers; however, the relationship between ZFHX3 and m6A modification is largely unknown in PCa. In this study, we found that ZFHX3 knockdown decreased total m6A levels through enhancing the transcriptional activity of FTO in PCa cells. Importantly, FTO inhibition suppressed cell proliferation and rescued the promoting function of ZFHX3 knockdown on cell proliferation. In vivo, we verified that FTO was upregulated and ZFHX3 was decreased in PCa patients and that a high level of ZFHX3 is indispensable for low FTO expression and is correlated with better patient survival. Through transcriptome sequencing and Me-RIP sequencing, we revealed that E2F2 and CDKN2C were the direct targets of FTO-mediated m6A modification and ZFXH3 was required for the regulation of FTO on E2F2 and CDKN2C expression. Unexpectedly, we uncovered that ZFHX3 expression was in return regulated by FTO in a m6A-dependent way. These findings establish a novel crosstalk mechanism between ZFHX3 and FTO in prostatic tumorigenesis.
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