Regulation of PCGEM1 by p54/nrb in prostate cancer.
PCGEM1 is a long non-coding RNA (lncRNA) that is often upregulated in prostate cancer. However, little is known how PCGEM1 is regulated. In the present study, we show transcriptional regulation of PCGEM1 in response to androgen deprivation by p54/nrb. While ectopic expression of p54/nrb increases, suppression of p54/nrb by RNAi or knockout (KO) reduces PCGEM1. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1, leading to upregulation of the androgen receptor splice variant AR3 which has been shown to play a role in castration resistance. Finally, 3,3'-Diindolylmethane (DIM), a known chemoprevention agent, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of p54/nrb-mediated expression of PCGEM1 and AR3, contributing to castration resistance in prostate cancer.
Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
Tsui-Ting
TT
Ho
Department of Biochemistry, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
Jianguo
J
Huang
Department of Biochemistry, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|System Biosciences, Mountain View, CA, USA.
Nanjiang
N
Zhou
Department of Pulmonary Medicine, Tongji Hospital, Tongji University, Shanghai, China.
Ziqiang
Z
Zhang
Department of Biochemistry, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
Pratirodh
P
Koirala
Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
Xinchun
X
Zhou
System Biosciences, Mountain View, CA, USA.
Fangting
F
Wu
Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
Xianfeng
X
Ding
Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
Yin-Yuan
YY
Mo
RNA Biol. 2013 Jun;10(6):1003-8
23595112
Nat Genet. 2007 Mar;39(3):311-8
17277777
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12216-21
11050243
CA Cancer J Clin. 1972 Jul-Aug;22(4):232-40
4625049
J Natl Cancer Inst. 2015 Feb 06;107(4):null
25663692
J Cell Physiol. 2014 Mar;229(3):271-6
24037862
Mol Cell Biol. 1997 Feb;17(2):677-86
9001221
Hum Mol Genet. 2014 Apr 15;23(8):2132-44
24301678
Nucleic Acids Res. 2015 Feb 18;43(3):e17
25414344
Science. 1994 Feb 11;263(5148):808-11
8303297
J Clin Invest. 2010 Aug;120(8):2715-30
20644256
Mol Endocrinol. 2009 Aug;23(8):1147-60
19423654
DNA Cell Biol. 2006 Mar;25(3):135-41
16569192
Invest Ophthalmol Vis Sci. 2013 Jun 12;54(6):4007-15
23640037
Oncogene. 2016 Mar 17;35(11):1399-410
26148231
Nucleic Acids Res. 1997 Jun 15;25(12 ):2284-92
9171077
Biochem Biophys Res Commun. 2003 Jul 4;306(3):660-5
12810069
Mol Cell. 2013 Mar 28;49(6):1083-96
23395002
Nat Biotechnol. 2011 Jul 31;29(8):742-9
21804560
Cell. 2007 May 18;129(4):823-37
17512414
Mol Cell Biol. 2007 Jul;27(13):4863-75
17452459
Clin Cancer Res. 2011 Jun 15;17(12):3876-83
21680543
Nucleic Acids Res. 2016 Jan 4;44(D1):D203-8
26586799
Cell Death Dis. 2014 Jan 23;5:e1008
24457952
Mol Cell Biol. 1993 Sep;13(9):5593-603
8355702
N Engl J Med. 2014 Sep 11;371(11):1028-38
25184630
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16759-65
20823238
Carcinogenesis. 2011 Aug;32(8):1176-82
21642354
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3207-12
19202062
Nature. 2012 Jul 12;487(7406):239-43
22722839
J Mol Cell Biol. 2014 Jun;6(3):181-91
24721780
Nat Med. 2015 Nov;21(11):1253-61
26540387
FEBS Lett. 2002 Nov 6;531(2):109-14
12417296
Cancer Discov. 2011 Oct;1(5):391-407
22096659
Nucleic Acids Res. 2014 Jan;42(Database issue):D98-103
24285305
BMC Med Genomics. 2010 Sep 24;3:43
20868494
Nature. 2013 Aug 29;500(7464):598-602
23945587
Food Chem Toxicol. 1988 Jan;26(1):59-70
3278958
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
25559415
Cell Res. 2013 Mar;23(3):340-50
23208419
Mol Cells. 2013 Jan;35(1):61-9
23212346
Oncogene. 2004 Jan 15;23(2):605-11
14724589
Cancer Cell. 2007 Sep;12(3):215-29
17785203
Nature. 2015 Jan 29;517(7536):583-8
25494202
Nucleic Acids Res. 2012 Jan;40(Database issue):D210-5
22135294
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20314-9
18077367
Med Princ Pract. 2016;25 Suppl 2:11-7
26501150
Prostate. 2015 Feb;75(2):161-74
25307492
Cell Death Differ. 2013 Nov;20(11):1558-68
23933812
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W401-7
24861617
Oncotarget. 2016 Mar 29;7(13):15481-91
26848868
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4846-50
22416126