PARG suppresses tumorigenesis and downregulates genes controlling angiogenesis, inflammatory response, and immune cell recruitment.
3T3 Cells
Adenosine Diphosphate
Animals
Carcinogenesis
/ genetics
Down-Regulation
Fibroblasts
/ metabolism
Glycoside Hydrolases
/ genetics
Mice
Neoplasms
/ blood supply
Neovascularization, Pathologic
/ immunology
Poly Adenosine Diphosphate Ribose
/ metabolism
Poly(ADP-ribose) Polymerase Inhibitors
/ pharmacology
Poly(ADP-ribose) Polymerases
/ metabolism
Tumor Microenvironment
/ genetics
3 T3 cells
Doxycycline
PARG
PARP
Poly(ADP-ribose) glycohydrolase
Poly(ADP-ribose) polymerase
Poly(ADP-ribose), chemokines
Tumorigenesis
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
18 May 2022
18 May 2022
Historique:
received:
07
12
2021
accepted:
09
05
2022
entrez:
18
5
2022
pubmed:
19
5
2022
medline:
21
5
2022
Statut:
epublish
Résumé
Chemokines are highly expressed in tumor microenvironment and play a critical role in all aspects of tumorigenesis, including the recruitment of tumor-promoting immune cells, activation of cancer-associated fibroblasts, angiogenesis, metastasis, and growth. Poly (ADP-ribose) polymerase (PARP) is a multi-target transcription regulator with high levels of poly(ADP-ribose) (pADPr) being reported in a variety of cancers. Furthermore, poly (ADP-ribose) glycohydrolase (PARG), an enzyme that degrades pADPr, has been reported to be downregulated in tumor tissues with abnormally high levels of pADPr. In conjunction to this, we have recently reported that the reduction of pADPr, by either pharmacological inhibition of PARP or PARG's overexpression, disrupts renal carcinoma cell malignancy in vitro. Here, we use 3 T3 mouse embryonic fibroblasts, a universal model for malignant transformation, to follow the effect of PARG upregulation on cells' tumorigenicity in vivo. We found that the overexpression of PARG in mouse allografts produces significantly smaller tumors with a delay in tumor onset. As downregulation of PARG has also been implicated in promoting the activation of pro-inflammatory genes, we also followed the gene expression profile of PARG-overexpressing 3 T3 cells using RNA-seq approach and observed that chemokine transcripts are significantly reduced in those cells. Our data suggest that the upregulation of PARG may be potentially useful for the tumor growth inhibition in cancer treatment and as anti-inflammatory intervention.
Identifiants
pubmed: 35585513
doi: 10.1186/s12885-022-09651-9
pii: 10.1186/s12885-022-09651-9
pmc: PMC9118775
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Poly Adenosine Diphosphate Ribose
26656-46-2
Adenosine Diphosphate
61D2G4IYVH
Poly(ADP-ribose) Polymerases
EC 2.4.2.30
Glycoside Hydrolases
EC 3.2.1.-
poly ADP-ribose glycohydrolase
EC 3.2.1.143
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
557Informations de copyright
© 2022. The Author(s).
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