AT-rich interaction domain 5A regulates the transcription of interleukin-6 gene in prostate cancer cells.
ARID5A
CRISPR-SAM
IL-6
histone modification
transcriptional regulation
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
24
09
2021
received:
01
07
2021
accepted:
29
09
2021
pubmed:
12
10
2021
medline:
23
2
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
Interleukin-6 (IL-6) is a pleiotropic cytokine that confers androgen-independence and aggressiveness in prostate cancer (PCa); however, the molecular mechanisms regulating IL-6 expression remain unclear. The expression of ARID5A, an AT-rich interaction domain (ARID) DNA-binding motif-containing transcription factor is positively correlated with IL-6 expression in human PCa. We, therefore, hypothesized that ARID5A could regulate IL-6 expression in PCa. The relationship between ARID5A and IL-6 in PCa patients was analyzed using statistical analyses of multiple clinical microarray data sets. To investigate whether ARID5A regulates IL-6 expression, CRISPR-driven ARID5A knockout clones were established in DU145 and PC-3 cells. Analysis of three microarray data sets showed a positive correlation between ARID5A and IL-6 expression. The expression of IL-6 in ARID5A knockout clones was significantly reduced compared with control clones in both PCa cell lines. Knockout of ARID5A did not result in any loss of IL-6 mRNA stability. Instead, we observed a significant decrease in the occupancy of both active RNA Polymerase II and the active histone mark, H3K4me3 at the IL-6 transcriptional start site in ARID5A knockout PCa cells, suggesting a role for transcriptional regulation. Our study demonstrated that loss of ARID5A downregulates the expression of IL-6 at the transcriptional level.
Sections du résumé
BACKGROUND
Interleukin-6 (IL-6) is a pleiotropic cytokine that confers androgen-independence and aggressiveness in prostate cancer (PCa); however, the molecular mechanisms regulating IL-6 expression remain unclear. The expression of ARID5A, an AT-rich interaction domain (ARID) DNA-binding motif-containing transcription factor is positively correlated with IL-6 expression in human PCa. We, therefore, hypothesized that ARID5A could regulate IL-6 expression in PCa.
METHODS
The relationship between ARID5A and IL-6 in PCa patients was analyzed using statistical analyses of multiple clinical microarray data sets. To investigate whether ARID5A regulates IL-6 expression, CRISPR-driven ARID5A knockout clones were established in DU145 and PC-3 cells.
RESULTS
Analysis of three microarray data sets showed a positive correlation between ARID5A and IL-6 expression. The expression of IL-6 in ARID5A knockout clones was significantly reduced compared with control clones in both PCa cell lines. Knockout of ARID5A did not result in any loss of IL-6 mRNA stability. Instead, we observed a significant decrease in the occupancy of both active RNA Polymerase II and the active histone mark, H3K4me3 at the IL-6 transcriptional start site in ARID5A knockout PCa cells, suggesting a role for transcriptional regulation.
CONCLUSIONS
Our study demonstrated that loss of ARID5A downregulates the expression of IL-6 at the transcriptional level.
Identifiants
pubmed: 34633095
doi: 10.1002/pros.24251
pmc: PMC8665135
mid: NIHMS1745597
doi:
Substances chimiques
ARID5A protein, human
0
DNA-Binding Proteins
0
Interleukin-6
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
97-106Subventions
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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