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Transcriptional repression and apoptosis influence the effect of APOBEC3A/3B functional polymorphisms on biliary tract cancer risk

ABSTRACT: Transcriptional repression and apoptosis influence the effect of APOBEC3A/3B functional polymorphisms on biliary tract cancer risk

PROVIDER: PRJNA700633 | ENA |

REPOSITORIES: ENA

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Transcriptional repression and apoptosis influence the effect of APOBEC3A/3B functional polymorphisms on biliary tract cancer risk

Project description:APOBEC3s-related somatic mutations are the predominant burden in biliary tract cancers (BTCs). Here, we reveal the effects and mechanisms of APOBEC3A/3B functional polymorphisms on cholangiocarcinoma and gallbladder cancer (GBC). rs2267401-G at the APOBEC3B promoter decreases cholangiocarcinoma risk but increased GBC risk. rs2267401-G confers a decreased APOBEC3B promoter activity in cholangiocarcinoma cells but an increased activity in GBC cells. rs12157810-C at the APOBEC3A promoter decreases the risk of BTCs. rs12157810-C up-regulated the promoter activity in both cells. APOBEC3A overexpression attenuates cancer evolution via causing apoptosis, in contrast to APOBEC3B. Inflammatory factors promote cancer evolution via interacting with transcriptional repressors regulating the APOBEC3A/3B promoters. ATAC-seq was used to identify the difference between transcriptional networks of cholangiocarcinoma and GBC.

2022-01-07 | GSE166372 | GEO

RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization

Project description:Macrophages acquire a pro-inflammatory M1 phenotype in response to microbial products or pro-inflammatory cytokines through incompletely understood molecular mechanisms. We recently described the induction of APOBEC3A-mediated cellular site-specific cytosine-to-uracil (C>U) RNA editing during M1 macrophage polarization. However, the functional significance of this RNA editing is unknown. Here, we find that cellular RNA editing by APOBEC3A can also be induced by influenza or Maraba virus infections in normal macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA Seq analyses show that APOBEC3A induces C>U RNA editing (range 7%-88%) of 209 exonic or UTR sites in 203 genes during M1 polarization of monocyte-derived macrophages. The highest level of deleterious protein-recoding C>U RNA editing is observed in THOC5, which encodes a key nuclear protein implicated in the export of mRNAs during M-CSF driven macrophage differentiation. Knockdown of APOBEC3A in M1 macrophages reduces pro-inflammatory IL6, IL23A, and IL12B gene expression, CD80 and CD86 surface protein expression, and TNF-α, IL-1β and IL-6 cytokine secretion, and increases glycolysis and glycolytic capacity. These results demonstrate that APOBEC3A cytidine deaminase plays an important role in transcriptomic and functional polarization of pro-inflammatory M1 macrophages.

2020-03-13 | GSE146867 | GEO

mRNA expression profiling of ERCP biliary brushings of malignant biliary strictures

Project description:Identification of differential gene expression uging endoscopic biliary brushings Bile duct brishings of benign biliary strictures and malignant biliary strictures, samples snap frozen in liquid nitrogen

2012-03-01 | E-GEOD-34166 | biostudies-arrayexpress

Transcription map of wheat chromosome 3B

Project description:To improve our understanding of the organization and regulation of the wheat gene space, we established the first transcription map of a wheat chromosome (3B) by hybridizing the newly developed INRA GDEC Triticum aestivum NimbleGen 12x40k unigenes microarray with BAC pools from a new version of the 3B physical map as well as with cDNA probes from five tissues at three developmental stages each. By hybridizing the BAC pools with the wheat NimbleGen 40K unigenes chip we managed to map almost 3000 unigenes on the wheat chromosome 3B BACs and to study the organization of the wheat gene space along chromosome 3B. The sequences of the unigenes helped to perform functional and evolutionary analyses of these unigenes. By hybridizing the 15 cDNA samples from five organs at three developmental stages each we established the expression profiles of more than 32000 wheat unigenes. Particularly we focused on the expression of the unigenes mapped on wheat chromosome 3B to perform coexpression analyses.

2011-11-03 | E-TABM-1095 | biostudies-arrayexpress

Prospectively-defined patterns of APOBEC3A mutagenesis are prevalent in human cancers

Project description:APOBEC3A mutagenesis

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Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA hypermutation.

Project description: Not available

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Primary Biliary Cirrhosis

Project description:Primary Biliary Cirrhosis

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3B-SEQ

Project description:Sequencing RNA-Seq of the bread wheat chromosome 3B

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Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease

Project description:Biliary diseases can cause inflammation, fibrosis, bile duct destruction and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have purified human Biliary Epithelial Cells (hBEC) from discarded human livers. hBECs were tested as a cell therapy in a mouse model of biliary disease where the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures and fibrosis. hBEC are expandable, phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.

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Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia.

Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.

2021-10-25 | GSE186444 | GEO

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