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AT‐rich interaction domain 5A regulates the transcription of interleukin‐6 gene in prostate cancer cells

Year: 2021
Type: article
Abstract: 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.
Source: The Prostate
DOI: 10.1002/pros.24251
Authors: Wataru Ikeuchi, Yuriko Wakita, Guoxiang Zhang, Chun Li, Keiichi Itakura, Takahiro Yamakawa
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W3206703616
FWCI: 1.916
Cites: 46
Cited by: 15
Related to: 10