Abstract
Introduction: DNA methylation regulates gene transcriptional functions in the pathogenesis of malignant diseases. In prostate cancer, several tumor suppressors are known to be tumor specifically methylated. Methods: In this study, 450K methylation data and mRNA expression data were accessed from The Cancer Genome Atlas-Prostate Adenocarcinoma database and analyzed bioinformatically. Methylation-specific PCR was used to examine the methylation condition in AOX1 promoter. qRT-PCR was applied to measure the mRNA expression of AOX1. Western blot was employed to detect the expressions of AOX1 and the EMT associated proteins. Transwell and scratch healing assays were used to examine the invasive and migratory abilities of the prostate cancer cells respectively. Results: AOX1 was lowly expressed and hypermethylated in the prostate cancer tissues and cells. Also, AOX1 was downregulated at protein level in prostate cancer cells. Knocking down AOX1 could promote cell migration and invasion in the prostate cancer cells. By using a DNA methylation inhibitor, 5-AzadC was found to promote the expression of AOX1 and reverse the promoting effects of short interfering RNA against AOX1 on cell migration and invasion. Conclusion: This study suggested that DNA methylation and low AOX1 level might be biomarkers for prostate cancer.
References
1.
Siegel
RL
, Miller
KD
, Jemal
A
. Cancer statistics, 2017
. CA Cancer J Clin
. 2017
;67
(1
):7
–30
.2.
Peyromaure
M
, Debre
B
, Mao
K
, Zhang
G
, Wang
Y
, Sun
Z
, . Management of prostate cancer in China: a multicenter report of 6 institutions
. J Urol
. 2005
;174
(5
):1794
–7
.3.
Tsai
HC
, Baylin
SB
. Cancer epigenetics: linking basic biology to clinical medicine
. Cell Res
. 2011
;21
(3
):502
–17
.4.
Bird
A
. DNA methylation patterns and epigenetic memory
. Genes Dev
. 2002
;16
(1
):6
–21
.5.
Feinberg
AP
. Epigenetics at the epicenter of modern medicine
. JAMA
. 2008
;299
(11
):1345
–50
.6.
Jones
PA
, Baylin
SB
. The fundamental role of epigenetic events in cancer
. Nat Rev Genet
. 2002
;3
(6
):415
–28
.7.
Chang
X
, Li
Z
, Ma
J
, Deng
P
, Zhang
S
, Zhi
Y
, . DNA methylation of NDRG2 in gastric cancer and its clinical significance
. Dig Dis Sci
. 2013
;58
(3
):715
–23
.8.
Cheng
D
, Deng
J
, Zhang
B
, He
X
, Meng
Z
, Li
G
, . LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation
. EBioMedicine
. 2018
;36
:159
–70
.9.
Lam
K
, Pan
K
, Linnekamp
JF
, Medema
JP
, Kandimalla
R
. DNA methylation based biomarkers in colorectal cancer: a systematic review
. Biochim Biophys Acta
. 2016
;1866
(1
):106
–20
.10.
Strand
SH
, Orntoft
TF
, Sorensen
KD
. Prognostic DNA methylation markers for prostate cancer
. Int J Mol Sci
. 2014
;15
(9
):16544
–76
.11.
Blute
ML
Jr, Damaschke
NA
, Jarrard
DF
. The epigenetics of prostate cancer diagnosis and prognosis: update on clinical applications
. Curr Opin Urol
. 2015
;25
(1
):83
–8
.12.
Esteller
M
, Corn
PG
, Baylin
SB
, Herman
JG
. A gene hypermethylation profile of human cancer
. Cancer Res
. 2001
;61
(8
):3225
–9
.13.
Roehl
KA
, Antenor
JA
, Catalona
WJ
. Serial biopsy results in prostate cancer screening study
. J Urol
. 2002
;167
(6
):2435
–9
.14.
Garattini
E
, Fratelli
M
, Terao
M
. The mammalian aldehyde oxidase gene family
. Hum Genomics
. 2009
;4
(2
):119
–30
.15.
Fagerberg
L
, Hallstrom
BM
, Oksvold
P
, Kampf
C
, Djureinovic
D
, Odeberg
J
, . Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
. Mol Cell Proteomics
. 2014
;13
(2
):397
–406
.16.
Kitamura
S
, Sugihara
K
, Ohta
S
. Drug-metabolizing ability of molybdenum hydroxylases
. Drug Metab Pharmacokinet
. 2006
;21
(2
):83
–98
.17.
Salmans
ML
, Zhao
F
, Andersen
B
. The estrogen-regulated anterior gradient 2 (AGR2) protein in breast cancer: a potential drug target and biomarker
. Breast Cancer Res
. 2013
;15
(2
):204
.18.
Atala
A
. Re: epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression
. J Urol
. 2020
;203
(4
):666
.19.
Zhang
H
, Liu
YP
, Ge
AQ
, Wang
X
, Sun
HR
, Bi
HR
, . Association between AOX1, IRF4 methylation in peripheral blood leukocyte DNA and the risks of breast cancer: a case-control study
. Zhonghua Liu Xing Bing Xue Za Zhi
. 2018
;39
(9
):1265
–9
.20.
Wu
TI
, Huang
RL
, Su
PH
, Mao
SP
, Wu
CH
, Lai
HC
. Ovarian cancer detection by DNA methylation in cervical scrapings
. Clin Epigenetics
. 2019
;11
(1
):166
.21.
Luo
X
, Huang
R
, Sun
H
, Liu
Y
, Bi
H
, Li
J
, . Methylation of a panel of genes in peripheral blood leukocytes is associated with colorectal cancer
. Sci Rep
. 2016
;6
:29922
.22.
Gevaert
O
. MethylMix: an R package for identifying DNA methylation-driven genes
. Bioinformatics
. 2015
;31
(11
):1839
–41
.23.
Albrecht
AL
, Singh
RK
, Somji
S
, Sens
MA
, Sens
DA
, Garrett
SH
. Basal and metal-induced expression of metallothionein isoform 1 and 2 genes in the RWPE-1 human prostate epithelial cell line
. J Appl Toxicol
. 2008
;28
(3
):283
–93
.24.
Jaworska
D
, Szliszka
E
. Targeting apoptotic activity against prostate cancer stem cells
. Int J Mol Sci
. 2017
;18
(8
):1648
.25.
Zhang
X
, Hu
X
, Mu
S
, Zhan
Y
, An
Q
, Liu
Z
, . Apogossypolone inhibits the proliferation of LNCaP cells in vitro and in vivo
. Mol Med Rep
. 2014
;10
(3
):1184
–94
.26.
Moller
M
, Strand
SH
, Mundbjerg
K
, Liang
G
, Gill
I
, Haldrup
C
, . Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients
. Sci Rep
. 2017
;7
:40636
.27.
Vantaku
V
, Putluri
V
, Bader
DA
, Maity
S
, Ma
J
, Arnold
JM
, . Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression
. Oncogene
. 2020
;39
(40
):6265
–85
.28.
Saitoh
M
. Involvement of partial EMT in cancer progression
. J Biochem
. 2018
;164
(4
):257
–64
.29.
Moore
LD
, Le
T
, Fan
G
. DNA methylation and its basic function
. Neuropsychopharmacology
. 2013
;38
(1
):23
–38
.30.
Yan
H
, Guan
Q
, He
J
, Lin
Y
, Zhang
J
, Li
H
, . Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues
. J Transl Med
. 2017
;15
(1
):26
.31.
Lounglaithong
K
, Bychkov
A
, Sampatanukul
P
. Aberrant promoter methylation of the PAQR3 gene is associated with prostate cancer
. Pathol Res Pract
. 2018
;214
(1
):126
–9
.32.
Zhou
X
, Jiao
D
, Dou
M
, Chen
J
, Li
Z
, Li
Y
, . Association of glutathione-S-transferase p1 gene promoter methylation and the incidence of prostate cancer: a systematic review and meta-analysis
. J Cancer Res Clin Oncol
. 2019
;145
(8
):1939
–48
.33.
Horvath
S
, Raj
K
. DNA methylation-based biomarkers and the epigenetic clock theory of ageing
. Nat Rev Genet
. 2018
;19
(6
):371
–84
.34.
Wang
Z
, Li
X
, Klaunig
JE
. Investigation of the mechanism of triclosan induced mouse liver tumors
. Regul Toxicol Pharmacol
. 2017
;86
:137
–47
.35.
Haldrup
C
, Mundbjerg
K
, Vestergaard
EM
, Lamy
P
, Wild
P
, Schulz
WA
, . DNA methylation signatures for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer
. J Clin Oncol
. 2013
;31
(26
):3250
–8
.© 2022 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2022
You do not currently have access to this content.
