Abstract
Introduction: Bladder cancer (BC) is a common malignant tumor in the urinary system with high mortality and recurrence rates. This study sought to identify crucial circular RNAs (circRNAs) associated with BC. Methods: The mRNA, miRNA, and circRNA expression profiles of BC were downloaded from GEO database. The differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified using bioinformatics method. Combining circRNA-miRNA pairs with miRNA-mRNA pairs, the competing endogenous RNA (ceRNA; DEcircRNA-DEmi-RNA-DEmRNA) regulatory network was constructed. Functional annotation of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network were performed. qRT-PCR validation was performed. Results: A total of 4,003 DEmRNAs, 25 DEmiRNAs, and 119 DEcircRNAs were obtained. The ceRNA network contained 18 circRNA-miRNA pairs and 699 mi-RNA-mRNA pairs, including 17 circRNAs, 4 miRNAs, and 624 mRNAs. Functional annotation of DEmRNAs in ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in glycerolipid metabolism, p53 signaling pathway, and oocyte meiosis. Except for hsa_circ_0028173, expression of the others in the qRT-PCR results was consistent with that in our integrated analysis, generally. Conclusion: We speculate that hsa_circ_0008035/hsa-miR-107/MSRB3 and hsa_circ_0028173/hsa-miR-338-3p/TPX2/GATA3 interaction pairs may play a vital role in BC.
References
1.
Liu
L
, Wu
SQ
, Zhu
X
, Xu
R
, Ai
K
, Zhang
L
, et al. Analysis of ceRNA network identifies prognostic circRNA biomarkers in bladder cancer
. Neoplasma
. 2019
;66
(5
):736
–45
. .2.
Li
F
, Yu
Z
, Chen
P
, Lin
G
, Li
T
, Hou
L
, et al. The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer
. Am J Cancer Res
. 2016
;6
(2
):331
–40
..3.
Inamura
K
. Bladder cancer: new insights into its molecular pathology
. Cancers
. 2018
;10
(4
):100
..4.
Chi
H
, Yang
R
, Zheng
X
, Zhang
L
, Jiang
R
, Chen
J
. LncRNA RP11–79H23.3 functions as a competing endogenous RNA to regulate PTEN expression through sponging hsa-miR-107 in the development of bladder cancer
. Inter J Mol Sci
. 2018
;19
(9
):2531
..5.
Chen
G
, Wang
Q
, Yang
Q
, Li
Z
, Du
Z
, Ren
M
, et al. Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma
. PLoS One
. 2018
;13
(8
):e0202896
. .6.
Lu
HC
, Yao
JQ
, Yang
X
, Han
J
, Wang
JZ
, Xu
K
, et al. Identification of a potentially functional circRNA-miRNA-mRNA regulatory network for investigating pathogenesis and providing possible biomarkers of bladder cancer
. Cancer Cell Int
. 2020
;20
:31
. .7.
Gao
X
, Chen
Y
, Chen
M
, Wang
S
, Wen
X
, Zhang
S
. Identification of key candidate genes and biological pathways in bladder cancer
. PeerJ
. 2018
;6
:e6036
. .8.
Kwak
GH
, Kim
HY
. MsrB3 deficiency induces cancer cell apoptosis through p53-independent and ER stress-dependent pathways
. Arch Biochem Biophys
. 2017
;621
:1
–5
. .9.
Ma
X
, Wang
J
, Zhao
M
, Huang
H
, Wu
J
. Increased expression of methionine sulfoxide reductases B3 is associated with poor prognosis in gastric cancer
. Oncol Lett
. 2019
;18
(1
):465
–71
. .10.
Aakula
A
, Kohonen
P
, Leivonen
SK
, Mäkelä
R
, Hintsanen
P
, Mpindi
JP
, et al. Systematic identification of microRNAs that impact on proliferation of prostate cancer cells and display changed expression in tumor tissue
. Eur Urol
. 2016
;69
(6
):1120
–8
. .11.
Ye
X
, Liang
T
, Deng
C
, Li
Z
, Yan
D
. MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress
. Pathol Res Pract
. 2020
;216
(2
):152780
. .12.
Zhang
S
, Zang
D
, Cheng
Y
, Li
Z
, Yang
B
, Guo
T
, et al. Identification of key gene and pathways for the prediction of peritoneal metastasis of gastric cancer by co-expression analysis
. J Cancer
. 2020
;11
(10
):3041
–51
. .13.
Feng
Y
, Jiang
Y
, Wen
T
, Meng
F
, Shu
X
. Identifying potential prognostic markers for muscle-invasive bladder urothelial carcinoma by weighted gene co-expression network analysis
. Pathol Oncol Res
. 2020
;26
(2
):1063
–72
.14.
Su
H
, Tao
T
, Yang
Z
, Kang
X
, Zhang
X
, Kang
D
, et al. Circular RNA cTFRC acts as the sponge of MicroRNA-107 to promote bladder carcinoma progression
. Mol Cancer
. 2019
;18
(1
):27
. .15.
Zhong
Z
, Lv
M
, Chen
J
. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma
. Sci Rep
. 2016
;6
:30919
. .16.
Huang
S
, Zhang
X
, Guan
B
, Sun
P
, Hong
CT
, Peng
J
, et al. A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis
. Am J Transl Res
. 2019
;11
(4
):2455
–62
..17.
Li
C
, Tian
Y
, Liang
Y
, Li
Q
. Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis
. Cancer Cell Int
. 2020
;20
:84
. .18.
Shi
J
, Zhang
P
, Liu
L
, Min
X
, Xiao
Y
. Weighted gene coexpression network analysis identifies a new biomarker of CENPF for prediction disease prognosis and progression in nonmuscle invasive bladder cancer
. Mol Genet Genomic Med
. 2019
;7
(11
):e982
. .19.
Li
F
, Su
M
, Zhao
H
, Xie
W
, Cao
S
, Xu
Y
, et al. HnRNP-F promotes cell proliferation by regulating TPX2 in bladder cancer
. Am J Transl Res
. 2019
;11
(11
):7035
–48
.20.
Yan
L
, Li
Q
, Yang
J
, Qiao
B
. TPX2-p53-GLIPR1 regulatory circuitry in cell proliferation, invasion, and tumor growth of bladder cancer
. J Cell Biochem
. 2018
;119
(2
):1791
–803
. .21.
Yan
L
, Li
S
, Xu
C
, Zhao
X
, Hao
B
, Li
H
, et al. Target protein for Xklp2 (TPX2), a microtubule-related protein, contributes to malignant phenotype in bladder carcinoma
. Tumour Biol
. 2013
;34
(6
):4089
–100
. .22.
Li
S
, Liu
X
, Liu
T
, Meng
X
, Yin
X
, Fang
C
, et al. Identification of biomarkers correlated with the TNM staging and overall survival of patients with bladder cancer
. Front Physiol
. 2017
;8
:947
. .23.
Li
Y
, Ishiguro
H
, Kawahara
T
, Kashiwagi
E
, Izumi
K
, Miyamoto
H
. Loss of GATA3 in bladder cancer promotes cell migration and invasion
. Cancer Biol Ther
. 2014
;15
(4
):428
–35
. .24.
Dadhania
V
, Zhang
M
, Zhang
L
, Bondaruk
J
, Majewski
T
, Siefker-Radtke
A
, et al. Meta-analysis of the luminal and basal subtypes of bladder cancer and the identification of signature immunohistochemical markers for clinical use
. EBioMedicine
. 2016
;12
:105
–17
. .25.
Sun
F
, Yu
M
, Yu
J
, Liu
Z
, Zhou
X
, Liu
Y
, et al. miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B
. Cell Death Dis
. 2018
;9
(5
):522
. .26.
27.
Zou
T
, Duan
J
, Liang
J
, Shi
H
, Zhen
T
, Li
H
, et al. miR-338–3p suppresses colorectal cancer proliferation and progression by inhibiting MACC1
. Int J Clin Exp Pathol
. 2018
;11
(4
):2256
–67
..28.
Zhang
L
, Yan
R
, Zhang
SN
, Zhang
HZ
, Ruan
XJ
, Cao
Z
, et al. MicroRNA-338–3p inhibits the progression of bladder cancer through regulating ETS1 expression
. Eur Rev Med Pharmacol Sci
. 2019
;23
(5
):1986
–95
. .29.
Wang
Z
, Katsaros
D
, Biglia
N
, Shen
Y
, Fu
Y
, Tiirikainen
M
, et al. Low expression of WWC1, a tumor suppressor gene, is associated with aggressive breast cancer and poor survival outcome
. FEBS Open Bio
. 2019
;9
(7
):1270
–80
. .30.
Huang
Z
, Wang
X
, Ma
L
, Guo
Z
, Liu
H
, Du
M
, et al. Genetic variations in Hippo pathway genes influence bladder cancer risk in a Chinese population
. Arch Toxicol
. 2020
;94
(3
):785
–94
. .31.
Mares
J
, Szakacsova
M
, Soukup
V
, Duskova
J
, Horinek
A
, Babjuk
M
. Prediction of recurrence in low and intermediate risk non-muscle invasive bladder cancer by real-time quantitative PCR analysis: cDNA microarray results
. Neoplasma
. 2013
;60
(3
):295
–301
. .32.
Liu
Q
, Zhao
S
, Su
PF
, Yu
S
. Gene and isoform expression signatures associated with tumor stage in kidney renal clear cell carcinoma
. BMC Syst Biol
. 2013
;7
(Suppl 5
):S7
. .33.
Warnecke-Eberz
U
, Metzger
R
, Hölscher
AH
, Drebber
U
, Bollschweiler
E
. Diagnostic marker signature for esophageal cancer from transcriptome analysis
. Tumour Biol
. 2016
;37
(5
):6349
–58
. .34.
Wei
J
, Wang
J
, Gao
X
, Qi
F
. Identification of differentially expressed circRNAs and a novel hsa_circ_0000144 that promote tumor growth in gastric cancer
. Cancer Cell Inter
. 2019
;19
:268
. .35.
Mi
L
, Lei
L
, Yin
X
, Li
N
, Shi
J
, Han
X
, et al. Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A
. Biosci Rep
. 2020
;40
(8
):BSR20201313
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