Research Article

Histone Modifier Differentially Regulates Gene Expression and Unravels Survival Role of MicroRNA-494 in Jurkat Leukemia

Author(s): Arathi Jayaraman, Tong Zhou and Sundararajan Jayaraman*

Volume 10, Issue 1, 2021

Published on: 12 April, 2021

Page: [39 - 50] Pages: 12

DOI: 10.2174/2211536610666210412153322

Price: $65

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.

Keywords: Apoptosis, epigenetics, histone deacetylases, leukemia, microRNA-494, T cell, Trichostatin A.

Graphical Abstract
[1]
Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet 2016; 17(8): 487-500.
[http://dx.doi.org/10.1038/nrg.2016.59] [PMID: 27346641]
[2]
Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010; 70: 27-56.
[http://dx.doi.org/10.1016/B978-0-12-380866-0.60002-2] [PMID: 20920744]
[3]
Bird A. Genetic determinants of the epigenome in development and cancer. Swiss Med Wkly 2017; 147: w14523.
[PMID: 29039625]
[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): 1753-63.
[http://dx.doi.org/10.2217/epi-2019-0015] [PMID: 31755306]
[5]
Grunstein M. Histone acetylation in chromatin structure and transcription. Nature 1997; 389(6649): 349-52.
[http://dx.doi.org/10.1038/38664] [PMID: 9311776]
[6]
Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem 2001; 70: 81-120.
[http://dx.doi.org/10.1146/annurev.biochem.70.1.81] [PMID: 11395403]
[7]
Yoshida M, Matsuyama A, Komatsu Y, Nishino N. From discovery to the coming generation of histone deacetylase inhibitors. Curr Med Chem 2003; 10(22): 2351-8.
[http://dx.doi.org/10.2174/0929867033456602] [PMID: 14529478]
[8]
de Ruijter AJM, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone Deacetylases (HDACs): Characterization of the classical HDAC family. Biochem J 2003; 370(Pt 3): 737-49.
[http://dx.doi.org/10.1042/bj20021321] [PMID: 12429021]
[9]
Roche J, Bertrand P. Inside HDACs with more selective HDAC inhibitors. Eur J Med Chem 2016; 121: 451-83.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.047] [PMID: 27318122]
[10]
Marks PA, Richon VM, Breslow R, Rifkind RA. Histone deacetylase inhibitors as new cancer drugs. Curr Opin Oncol 2001; 13(6): 477-83.
[http://dx.doi.org/10.1097/00001622-200111000-00010] [PMID: 11673688]
[11]
Jayaraman A, Avgush K, Kulam R, et al. Treatment of autoimmune encephalomyelitis with a histone deacetylase inhibitor. Analyzing the role of immune-response genes. Free Neuropathol 2020; 1: 19.
[12]
Patel T, Patel V, Singh R, Jayaraman S. Chromatin remodeling resets the immune system to protect against autoimmune diabetes in mice. Immunol Cell Biol 2011; 89(5): 640-9.
[http://dx.doi.org/10.1038/icb.2010.144] [PMID: 21321581]
[13]
Jayaraman S, Patel A, Jayaraman A, Patel V, Holterman M, Prabhakar B. Transcriptome analysis of epigenetically modulated genome indicates signature genes in manifestation of type 1 diabetes and its prevention in NOD mice. PLoS One 2013; 8(1): e55074.
[http://dx.doi.org/10.1371/journal.pone.0055074] [PMID: 23383062]
[14]
Jayaraman A, Soni A, Prabhakar BS, Holterman M, Jayaraman S. The epigenetic drug Trichostatin A ameliorates experimental autoimmune encephalomyelitis via T cell tolerance induction and impaired influx of T cells into the spinal cord. Neurobiol Dis 2017; 108: 1-12.
[http://dx.doi.org/10.1016/j.nbd.2017.07.015] [PMID: 28736194]
[15]
Ambros V. microRNAs: Tiny regulators with great potential. Cell 2001; 107(7): 823-6.
[http://dx.doi.org/10.1016/S0092-8674(01)00616-X] [PMID: 11779458]
[16]
Bartel DP. Metazoan MicroRNAs. Cell 2018; 173(1): 20-51.
[http://dx.doi.org/10.1016/j.cell.2018.03.006] [PMID: 29570994]
[17]
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nat Rev Genet 2011; 12(2): 99-110.
[http://dx.doi.org/10.1038/nrg2936] [PMID: 21245828]
[18]
Sun HB, Chen X, Ji H, et al. miR‑494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol 2014; 45(6): 2486-94.
[http://dx.doi.org/10.3892/ijo.2014.2665] [PMID: 25270723]
[19]
Li X-T, Wang H-Z, Wu Z-W, et al. miR-494-3p regulates cellular proliferation, invasion, migration, and apoptosis by PTEN/AKT signaling in human glioblastoma cells. Cell Mol Neurobiol 2015; 35(5): 679-87.
[http://dx.doi.org/10.1007/s10571-015-0163-0] [PMID: 25662849]
[20]
Yang YK, Xi WY, Xi RX, Li JY, Li Q, Gao YE. MicroRNA-494 promotes cervical cancer proliferation through the regulation of PTEN. Oncol Rep 2015; 33(5): 2393-401.
[http://dx.doi.org/10.3892/or.2015.3821] [PMID: 25738254]
[21]
Romano G, Acunzo M, Garofalo M, et al. MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci USA 2012; 109(41): 16570-5.
[http://dx.doi.org/10.1073/pnas.1207917109] [PMID: 23012423]
[22]
Diakos C, Zhong S, Xiao Y, et al. TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a. Blood 2010; 116(23): 4885-93.
[http://dx.doi.org/10.1182/blood-2009-02-206706] [PMID: 20807887]
[23]
Ohdaira H, Sekiguchi M, Miyata K, Yoshida K. MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif 2012; 45(1): 32-8.
[http://dx.doi.org/10.1111/j.1365-2184.2011.00798.x] [PMID: 22151897]
[24]
Xiong R, Wang Z, Zhao Z, et al. MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration. Neurobiol Aging 2014; 35(3): 705-14.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.027] [PMID: 24269020]
[25]
Bai Y, Sun Y, Peng J, et al. Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494. Oncotarget 2014; 5(17): 7760-75.
[http://dx.doi.org/10.18632/oncotarget.2305] [PMID: 25226615]
[26]
Zhang R, Chen X, Zhang S, et al. Upregulation of miR-494 Inhibits cell growth and invasion and induces cell apoptosis by targeting cleft lip and palate transmembrane 1-like in esophageal squamous cell carcinoma. Dig Dis Sci 2015; 60(5): 1247-55.
[http://dx.doi.org/10.1007/s10620-014-3433-7] [PMID: 25480402]
[27]
Libório-Kimura TN, Jung HM, Chan EK. miR-494 represses HOXA10 expression and inhibits cell proliferation in oral cancer. Oral Oncol 2015; 51(2): 151-7.
[http://dx.doi.org/10.1016/j.oraloncology.2014.11.019] [PMID: 25500095]
[28]
Yang A, Wang X, Yu C, et al. microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer. Oncol Lett 2017; 14(3): 3177-84.
[http://dx.doi.org/10.3892/ol.2017.6501] [PMID: 28927063]
[29]
Autin P, Blanquart C, Fradin D. Epigenetic drugs for cancer and microRNAs: A focus on histone deacetylase inhibitors. Cancers (Basel) 2019; 11(10): 1530.
[http://dx.doi.org/10.3390/cancers11101530] [PMID: 31658720]
[30]
Jayaraman S. Flow cytometric determination of mitochondrial membrane potential changes during apoptosis of T lymphocytic and pancreatic beta cell lines: Comparison of tetramethylrhodamineethylester (TMRE), chloromethyl-X-rosamine (H2-CMX-Ros) and MitoTracker Red 580 (MTR580). J Immunol Methods 2005; 306(1-2): 68-79.
[http://dx.doi.org/10.1016/j.jim.2005.07.024] [PMID: 16256133]
[31]
Jayaraman AK, Jayaraman S. Increased level of exogenous zinc induces cytotoxicity and up-regulates the expression of the ZnT-1 zinc transporter gene in pancreatic cancer cells. J Nutr Biochem 2011; 22(1): 79-88.
[http://dx.doi.org/10.1016/j.jnutbio.2009.12.001] [PMID: 20392624]
[32]
Geiss GK, Bumgarner RE, Birditt B, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 2008; 26(3): 317-25.
[http://dx.doi.org/10.1038/nbt1385] [PMID: 18278033]
[33]
Van Lint C, Emiliani S, Verdin E. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr 1996; 5(4-5): 245-53.
[PMID: 8723390]
[34]
Wang Y, Wu X, Zhong Y, et al. Effects of histone deacetylase inhibition on the survival, proliferation and migration of Schwann cells, as well as on the expression of neurotrophic factors and genes associated with myelination. Int J Mol Med 2014; 34(2): 599-605.
[http://dx.doi.org/10.3892/ijmm.2014.1792] [PMID: 24888454]
[35]
Dhein J, Walczak H, Bäumler C, Debatin KM, Krammer PH. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 1995; 373(6513): 438-41.
[http://dx.doi.org/10.1038/373438a0] [PMID: 7530335]
[36]
Holtzman MJ, Green JM, Jayaraman S, Arch RH. Regulation of T cell apoptosis. Apoptosis 2000; 5(5): 459-71.
[http://dx.doi.org/10.1023/A:1009657321461] [PMID: 11256889]
[37]
Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells. Immunol Rev 2003; 193: 70-81.
[http://dx.doi.org/10.1034/j.1600-065X.2003.00051.x] [PMID: 12752672]
[38]
Weiler J, Hunziker J, Hall J. Anti-miRNA oligonucleotides (AMOs): Ammunition to target miRNAs implicated in human disease? Gene Ther 2006; 13(6): 496-502.
[http://dx.doi.org/10.1038/sj.gt.3302654] [PMID: 16195701]
[39]
Singh R, Bassett E, Chakravarti A, Parthun MR. Replication-dependent histone isoforms: A new source of complexity in chromatin structure and function. Nucleic Acids Res 2018; 46(17): 8665-78.
[http://dx.doi.org/10.1093/nar/gky768] [PMID: 30165676]
[40]
Zhu Y, Paniccia A, Schulick AC, et al. Identification of CD112R as a novel checkpoint for human T cells. J Exp Med 2016; 213(2): 167-76.
[http://dx.doi.org/10.1084/jem.20150785] [PMID: 26755705]
[41]
Xu R, Feng F, Yu X, Liu Z, Lao L. LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma. Cell Prolif 2018; 51(6): e12515.
[http://dx.doi.org/10.1111/cpr.12515] [PMID: 30152090]
[42]
Klec C, Prinz F, Pichler M. Involvement of the long noncoding RNA NEAT1 in carcinogenesis. Mol Oncol 2019; 13(1): 46-60.
[http://dx.doi.org/10.1002/1878-0261.12404] [PMID: 30430751]
[43]
Hildick-Smith GJ, Cooney JD, Garone C, et al. Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4. Am J Hum Genet 2013; 93(5): 906-14.
[http://dx.doi.org/10.1016/j.ajhg.2013.09.011] [PMID: 24119684]
[44]
Gomez-Cambronero J, Keire P, Phospholipase D. Phospholipase D: A novel major player in signal transduction. Cell Signal 1998; 10(6): 387-97.
[http://dx.doi.org/10.1016/S0898-6568(97)00197-6] [PMID: 9720761]
[45]
Goto K, Doi M, Wang T, Kunisue S, Murai I, Okamura H. G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review Endocr J 2017; 64(6): 571-9.
[http://dx.doi.org/10.1507/endocrj.EJ17-0130] [PMID: 28502923]
[46]
Wang L, Fu TM, Zhou Y, Xia S, Greka A, Wu H. Structures and gating mechanism of human TRPM2. Science 2018; 362(6421): eaav4809.
[http://dx.doi.org/10.1126/science.aav4809] [PMID: 30467180]
[47]
Kos J, Lah TT. Cysteine proteinases and their endogenous inhibitors: Target proteins for prognosis, diagnosis and therapy in cancer (review). Oncol Rep 1998; 5(6): 1349-61.
[http://dx.doi.org/10.3892/or.5.6.1349] [PMID: 9769367]
[48]
Singh B, Carpenter G, Coffey RJ. EGF receptor ligands: Recent advances. F1000Res 2016; 5(F1000 Faculty Rev): 2270.
[http://dx.doi.org/10.12688/f1000research.9025.1]
[49]
Miranda KC, Huynh T, Tay Y, et al. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 2006; 126(6): 1203-17.
[http://dx.doi.org/10.1016/j.cell.2006.07.031] [PMID: 16990141]
[50]
Teixeiro E, Daniels MA. ERK and cell death: ERK location and T cell selection. FEBS J 2010; 277(1): 30-8.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07368.x] [PMID: 19843172]
[51]
Tosello V, Bordin F, Yu J, et al. Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation. Leukemia 2016; 30(4): 812-22.
[http://dx.doi.org/10.1038/leu.2015.335] [PMID: 26648536]
[52]
Paolino M, Penninger JM. CBL-b in T-cell activation. Semin Immunopathol 2010; 32(2): 137-48.
[http://dx.doi.org/10.1007/s00281-010-0197-9] [PMID: 20458601]
[53]
Liu X, Chen X, Yu X, et al. Regulation of microRNAs by epigenetics and their interplay involved in cancer. J Exp Clin Cancer Res 2013; 32(1): 96.
[http://dx.doi.org/10.1186/1756-9966-32-96] [PMID: 24261995]
[54]
Yu J, Wang F, Yang GH, et al. Human microRNA clusters: Genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun 2006; 349(1): 59-68.
[http://dx.doi.org/10.1016/j.bbrc.2006.07.207] [PMID: 16934749]
[55]
Zhang X, Zhao X, Fiskus W, et al. Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas. Cancer Cell 2012; 22(4): 506-23.
[http://dx.doi.org/10.1016/j.ccr.2012.09.003] [PMID: 23079660]
[56]
Zisoulis DG, Kai ZS, Chang RK, Pasquinelli AE. Autoregulation of microRNA biogenesis by let-7 and argonaute. Nature 2012; 486(7404): 541-4.
[http://dx.doi.org/10.1038/nature11134] [PMID: 22722835]
[57]
Turner MJ, Jiao AL, Slack FJ. Autoregulation of lin-4 microRNA transcription by RNA activation (RNAa) in C. elegans. Cell Cycle 2014; 13(5): 772-81.
[http://dx.doi.org/10.4161/cc.27679] [PMID: 24398561]
[58]
Sanchez-Correa B, Valhondo I, Hassouneh F, et al. DNAM-1 and the TIGIT/PVRIG/TACTILE axis: Novel immune checkpoints for natural killer cell-based cancer immunotherapy. Cancers (Basel) 2019; 11(6): 877.
[http://dx.doi.org/10.3390/cancers11060877] [PMID: 31234588]
[59]
Shen PF, Chen XQ, Liao YC, et al. MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate 2014; 74(7): 756-67.
[http://dx.doi.org/10.1002/pros.22795] [PMID: 24644030]
[60]
Zhou RP, Chen G, Shen ZL, Pan LQ. Cinobufacin suppresses cell proliferation via miR-494 in BGC- 823 gastric cancer cells. Asian Pac J Cancer Prev 2014; 15(3): 1241-5.
[http://dx.doi.org/10.7314/APJCP.2014.15.3.1241] [PMID: 24606447]
[61]
Asuthkar S, Velpula KK, Nalla AK, Gogineni VR, Gondi CS, Rao JS. Irradiation-induced angiogenesis is associated with an MMP-9-miR-494-syndecan-1 regulatory loop in medulloblastoma cells. Oncogene 2014; 33(15): 1922-33.
[http://dx.doi.org/10.1038/onc.2013.151] [PMID: 23728345]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy