The up-stream regulation of polymerase-1 and transcript release factor(PTRF/Cavin-1) in prostate cancer: an epigenetic analysis

Jin-Yih Low; Helen D. Nicholson; Jin-Yih Low; Helen D. Nicholson

doi:10.3934/molsci.2016.3.466

AIMS Molecular Science

2016, Volume 3, Issue 3: 466-478. doi: 10.3934/molsci.2016.3.466

Previous Article Next Article

Research article Topical Sections

The up-stream regulation of polymerase-1 and transcript release factor(PTRF/Cavin-1) in prostate cancer: an epigenetic analysis

Jin-Yih Low ^,,
Helen D. Nicholson

Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand

Received: 24 July 2016 Accepted: 14 September 2016 Published: 25 January 2016

The expression of PTRF is down-regulated in prostate cell lines and tissues. Restorationof PTRF expression leads to a reduction in aggressive phenotypes of prostate cancer cells both in vitro and in vivo. Epigenetics examines the changes in gene expression that occur without changing DNA sequences. Two main epigenetic mechanisms include hypermethylation of the gene’s promoter region and changes to the chromatin structure through histone modification. We investigated the involvement of possible epigenetic up-stream regulatory mechanisms that may down-regulate PTRF in prostate cancer cells. Normal (RWPE-1) and prostate cancer (LNCaP and PC3) cell lines were treated with DNA methylation inhibitor, 5-aza-2Ꞌ-deoxycytidine (5AZA) and histone deacetylase inhibitor, Trichostatin-A (TSA) either independently or in combination. A bioinformatics approach was also used to investigate the changes of epigenetic driver genes in silico. In normal prostate cells(RWPE-1), and androgen independent prostate cancer cells (PC3), treatment with 5AZA and/or TSA did not affect PTRF expression. However, TSA and TSA + 5AZA treatments, but not 5AZA alone,up-regulated the expression of PTRF in LNCaP cells. Bioinformatic analysis of the potential histone deacetylase (HDAC) genes involved showed that HDAC2, HDAC6 and HDAC10 may be potential candidate genes for the regulation of PTRF. This corroborative study describes the possible role of an epigenetic mechanism onPTRF, further studies are required to allow a better understanding of theup-stream mechanisms that regulate PTRF expression.
- DNA methylation,
- histone deacetylase,
- histone modification
Citation: Jin-Yih Low, Helen D. Nicholson. The up-stream regulation of polymerase-1 and transcript release factor(PTRF/Cavin-1) in prostate cancer: an epigenetic analysis[J]. AIMS Molecular Science, 2016, 3(3): 466-478. doi: 10.3934/molsci.2016.3.466

Related Papers:

Abstract

The expression of PTRF is down-regulated in prostate cell lines and tissues. Restorationof PTRF expression leads to a reduction in aggressive phenotypes of prostate cancer cells both in vitro and in vivo. Epigenetics examines the changes in gene expression that occur without changing DNA sequences. Two main epigenetic mechanisms include hypermethylation of the gene’s promoter region and changes to the chromatin structure through histone modification. We investigated the involvement of possible epigenetic up-stream regulatory mechanisms that may down-regulate PTRF in prostate cancer cells. Normal (RWPE-1) and prostate cancer (LNCaP and PC3) cell lines were treated with DNA methylation inhibitor, 5-aza-2Ꞌ-deoxycytidine (5AZA) and histone deacetylase inhibitor, Trichostatin-A (TSA) either independently or in combination. A bioinformatics approach was also used to investigate the changes of epigenetic driver genes in silico. In normal prostate cells(RWPE-1), and androgen independent prostate cancer cells (PC3), treatment with 5AZA and/or TSA did not affect PTRF expression. However, TSA and TSA + 5AZA treatments, but not 5AZA alone,up-regulated the expression of PTRF in LNCaP cells. Bioinformatic analysis of the potential histone deacetylase (HDAC) genes involved showed that HDAC2, HDAC6 and HDAC10 may be potential candidate genes for the regulation of PTRF. This corroborative study describes the possible role of an epigenetic mechanism onPTRF, further studies are required to allow a better understanding of theup-stream mechanisms that regulate PTRF expression.

References

[1]	Jemal A, Bray F, Center MM, et al. (2011) Global cancer statistics. CA Cancer J Clin 61: 69-90. doi: 10.3322/caac.20107
[2]	Jansa P, Mason SW, Hoffmann-Rohrer U, et al. (1998) Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. EMBO J 17: 2855-2864. doi: 10.1093/emboj/17.10.2855
[3]	Hill MM, Bastiani M, Luetterforst R, et al. (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132: 113-124. doi: 10.1016/j.cell.2007.11.042
[4]	Low JY, Nicholson HD (2014) Emerging role of polymerase-1 and transcript release factor (PTRF/ Cavin-1) in health and disease. Cell Tissue Res 357: 505-513. doi: 10.1007/s00441-014-1964-z
[5]	Gould ML, Williams G, Nicholson HD (2010) Changes in caveolae, caveolin, and polymerase 1 and transcript release factor (PTRF) expression in prostate cancer progression. Prostate 70: 1609-1621. doi: 10.1002/pros.21195
[6]	Aung CS, Hill MM, Bastiani M, et al. (2011) PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9. Eur J Cell Biol 90: 136-142. doi: 10.1016/j.ejcb.2010.06.004
[7]	Moon H, Lee CS, Inder KL, et al. (2014) PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer. Oncogene 33: 3561-3570. doi: 10.1038/onc.2013.315
[8]	Nassar ZD, Moon H, Duong T, et al. (2013) PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis. Oncotarget 4: 1844-1855. doi: 10.18632/oncotarget.1300
[9]	Nassar ZD, Parat MO (2015) Cavin Family: New Players in the Biology of Caveolae. Int Rev Cell Mol Biol 320: 235-305. doi: 10.1016/bs.ircmb.2015.07.009
[10]	Briand N, Dugail I, Le Lay S (2011) Cavin proteins: New players in the caveolae field. Biochimie 93: 71-77. doi: 10.1016/j.biochi.2010.03.022
[11]	Hansen CG, Bright NA, Howard G, et al. (2009) SDPR induces membrane curvature and functions in the formation of caveolae. Nat Cell Biol 11: 807-814. doi: 10.1038/ncb1887
[12]	McMahon KA, Zajicek H, Li WP, et al. (2009) SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function. EMBO J 28: 1001-1015. doi: 10.1038/emboj.2009.46
[13]	Tagawa M, Ueyama T, Ogata T, et al. (2008) MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis. Am J Physiol Cell Physiol 295: C490-498. doi: 10.1152/ajpcell.00188.2008
[14]	Bai L, Deng X, Li Q, et al. (2012) Down-regulation of the cavin family proteins in breast cancer. J Cell Biochem 113: 322-328. doi: 10.1002/jcb.23358
[15]	Zochbauer-Muller S, Fong KM, Geradts J, et al. (2005) Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation. Oncogene 24: 6249-6255. doi: 10.1038/sj.onc.1208775
[16]	Lee JH, Byun DS, Lee MG, et al. (2008) Frequent epigenetic inactivation of hSRBC in gastric cancer and its implication in attenuated p53 response to stresses. Int J Cancer 122: 1573-1584.
[17]	Lengauer C, Issa JP (1998) The role of epigenetics in cancer. DNA Methylation, Imprinting and the Epigenetics of Cancer--an American Association for Cancer Research Special Conference. Las Croabas, Puerto Rico, 12-16 1997 December. Mol Med Today 4: 102-103.
[18]	Verma M, Maruvada P, Srivastava S (2004) Epigenetics and cancer. Crit Rev Clin Lab Sci 41: 585-607. doi: 10.1080/10408360490516922
[19]	Verma M, Srivastava S (2002) Epigenetics in cancer: implications for early detection and prevention. Lancet Oncol 3: 755-763. doi: 10.1016/S1470-2045(02)00932-4
[20]	Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A 51: 786-794. doi: 10.1073/pnas.51.5.786
[21]	Jarrard DF, Bova GS, Ewing CM, et al. (1997) Deletional, mutational, and methylation analyses of CDKN2 (p16/MTS1) in primary and metastatic prostate cancer. Genes Chromosomes Cancer 19: 90-96.
[22]	Kong D, Ahmad A, Bao B, et al. (2012) Histone deacetylase inhibitors induce epithelial-to-mesenchymal transition in prostate cancer cells. PLoS One 7: e45045. doi: 10.1371/journal.pone.0045045
[23]	Ropero S, Esteller M (2007) The role of histone deacetylases (HDACs) in human cancer. Mol Oncol 1: 19-25. doi: 10.1016/j.molonc.2007.01.001
[24]	Liu L, Pilch PF (2008) A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization. J Biol Chem 283: 4314-4322. doi: 10.1074/jbc.M707890200
[25]	Cameron EE, Bachman KE, Myohanen S, et al. (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21: 103-107. doi: 10.1038/5047
[26]	Tian Q, Stepaniants SB, Mao M, et al. (2004) Integrated genomic and proteomic analyses of gene expression in Mammalian cells. Mol Cell Proteomics 3: 960-969. doi: 10.1074/mcp.M400055-MCP200
[27]	Saito A, Yamashita T, Mariko Y, et al. (1999) A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci U S A 96: 4592-4597. doi: 10.1073/pnas.96.8.4592
[28]	Bots M, Johnstone RW (2009) Rational combinations using HDAC inhibitors. Clin Cancer Res 15: 3970-3977. doi: 10.1158/1078-0432.CCR-08-2786
[29]	Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403: 41-45. doi: 10.1038/47412
[30]	Chervona Y, Costa M (2012) Histone modifications and cancer: biomarkers of prognosis? Am J Cancer Res 2: 589-597.
[31]	Hayashi YK, Matsuda C, Ogawa M, et al. (2009) Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest 119: 2623-2633. doi: 10.1172/JCI38660

Reader Comments

Your name:*

Email:*
© 2016 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)