Affiliation:
1. Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612,United States
Abstract
Background:
Although the protein-coding genes are subject to histone hyperacetylation-
mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell
leukemia Jurkat.
Objective:
To determine whether treatment with the histone modifier Trichostatin A could concurrently
alter the expression profiles of microRNAs and protein-coding genes.
Methods:
Changes in histone hyperacetylation and viability in response to drug treatment were analyzed,
respectively, using western blotting and flow cytometry. Paired global expression profiling
of microRNAs and coding genes was performed and highly regulated genes have been validated by
qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression
of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR,
flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA
inhibitors.
Results:
Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and
apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to
differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although
transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis
or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly,
miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor-
mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this prosurvival
effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses,
which mediated caspase-dependent apoptosis.
Conclusion:
Our results unravel a pro-survival function of miR-494 and its putative interaction
with the PVRIG gene and the apoptotic machinery in Jurkat cells.
Publisher
Bentham Science Publishers Ltd.
Subject
Orthopedics and Sports Medicine,Emergency Medicine,General Medicine
Reference61 articles.
1. Allis C.D.; Jenuwein T.; The molecular hallmarks of epigenetic control. Nat Rev Genet 2016,17(8),487-500
2. Kulis M.; Esteller M.; DNA methylation and cancer. Adv Genet 2010,70,27-56
3. Bird A.; Genetic determinants of the epigenome in development and cancer. Swiss Med Wkly 2017,147,w14523
4. Jayaraman A.; Jayaraman S.; DNA hypermethylation does not negatively impact the transcription of the TNF-α gene in an acute T- cell leukemia. Epigenomics 2019,11(16),1753-1763
5. Grunstein M.; Histone acetylation in chromatin structure and transcription. Nature 1997,389(6649),349-352
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