Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is one of the most serious malignancies worldwide, seriously affecting the survival and living quality of patients. Abnormal expression of microRNAs plays a pivotal role in the development and progression of tumor, while exosomes are usually involved in some biological functions as tools for the delivery of intercellular substances, including miRNAs. The purpose of our study was to investigate the impact of exosome miR-148a-3p expression on ESCC. Methods: qRT-PCR was used to examine the relative expression of miR-148a-3p in plasma exosomes and in vitro cells. Cell proliferation ability was tested by CCK-8; the migration and invasion function were tested using Transwell assay. The overall survival (OS) and cancer-specific survival rate of ESCC patients were calculated using the Kaplan-Meier method. Results: The expression of exosomal miR-148a-3p in ESCC patients’ plasma can clearly distinguish the survival rate, and the OS rate with high expression of exosomal miR-148a-3p is clearly higher than the patients with low expression. In cell function tests, the miR-148a-3p expression of ESCC cell lines was lower than in control group. After transfecting miR-148a-3p mimic, the proliferation, migration, and invasion ability of experimental group was reduced than the control group. Conclusions: Above experimental results explained that miR-148a-3p showed significant tumor inhibition function both in serum exosomes of ESCC patients and in functional tests of cancer cell lines in vitro, suggesting that exosome miR-148a-3p can inhibit tumor progression and has the potential to be used as an indicator of clinical ESCC diagnosis and prognosis.
Journal Section:
Clinical Study
References
1.
Uhlenhopp
DJ
, Then
EO
, Sunkara
T
, Gaduputi
V
. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors
. Clin J Gastroenterol
. 2020
;13
(6
):1010
–21
. 2.
Abnet
CC
, Arnold
M
, Wei
WQ
. Epidemiology of esophageal squamous cell carcinoma
. Gastroenterology
. 2018
;154
(2
):360
–73
. 3.
Pennathur
A
, Gibson
MK
, Jobe
BA
, Luketich
JD
. Oesophageal carcinoma
. Lancet
. 2013
;381
(9864
):400
–12
. 4.
Siegel
RL
, Miller
KD
, Fuchs
HE
, Jemal
A
. Cancer statistics, 2021
. CA Cancer J Clin
. 2021
;71
(1
):7
–33
. 5.
Behera
J
, Tyagi
N
. Exosomes: mediators of bone diseases, protection, and therapeutics potential
. Oncoscience
. 2018
;5
(5–6
):181
–95
. 6.
Carney
RP
, Hazari
S
, Rojalin
T
, Knudson
A
, Gao
T
, Tang
Y
, et al. Targeting tumor-associated exosomes with integrin-binding peptides
. Adv Biosyst
. 2017
;1
(5
):1600038
. 7.
Akers
JC
, Gonda
D
, Kim
R
, Carter
BS
, Chen
CC
. Biogenesis of Extracellular Vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies
. J Neuro Oncol
. 2013
;113
(1
):1
–11
. 8.
Mao
L
, Li
X
, Gong
S
, Yuan
H
, Jiang
Y
, Huang
W
, et al. Serum exosomes contain ECRG4 mRNA that suppresses tumor growth via inhibition of genes involved in inflammation, cell proliferation, and angiogenesis
. Cancer Gene Ther
. 2018
;25
(9–10
):248
–59
. 9.
Doyle
LM
, Wang
MZ
. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis
. Cells
. 2019
;8
(7
):727
. 10.
Kalluri
R
, LeBleu
VS
. The biology, function, and biomedical applications of exosomes
. Science
. 2020
;367
(6478
):eaau6977
. 11.
Valadi
H
, Ekström
K
, Bossios
A
, Sjöstrand
M
, Lee
JJ
, Lötvall
JO
. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
. Nat Cell Biol
. 2007
;9
(6
):654
–9
. 12.
Bartel
DP
. MicroRNAs: genomics, biogenesis, mechanism, and function
. Cell
. 2004
;116
(2
):281
–97
. 13.
Xu
Q
, Jiang
Y
, Yin
Y
, Li
Q
, He
J
, Jing
Y
, et al. A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1
. J Mol Cell Biol
. 2013
;5
(1
):3
–13
. 14.
Zhou
H
, He
Y
, Li
L
, Wu
C
, Hu
G
. Identification novel prognostic signatures for Head and Neck Squamous Cell Carcinoma based on ceRNA network construction and immune infiltration analysis
. Int J Med Sci
. 2021
;18
(5
):1297
–311
. 15.
Cheng
Y
, Wang
X
, Qi
P
, Liu
C
, Wang
S
, Wan
Q
, et al. Tumor microenvironmental competitive endogenous RNA network and immune cells act as robust prognostic predictor of acute myeloid leukemia
. Front Oncol
. 2021
;11
:584884
. 16.
Ardila
HJ
, Sanabria-Salas
MC
, Meneses
X
, Rios
R
, Huertas-Salgado
A
, Serrano
ML
. Circulating miR-141-3p, miR-143-3p and miR-200c-3p are differentially expressed in colorectal cancer and advanced adenomas
. Mol Clin Oncol
. 2019
;11
(2
):201
–7
. 17.
Wang
Y
, Hu
Y
, Guo
J
, Wang
L
. miR-148a-3p suppresses the proliferation and invasion of esophageal cancer by targeting DNMT1
. Genet Test Mol Biomark
. 2019
;23
(2
):98
–104
. 18.
NCBI Resource Coordinators
. Database resources of the national center for biotechnology information
. Nucleic Acids Res
. 2017
;45
(D1
):D12
–17
. 19.
Pan
W
, Zhu
S
, Yuan
M
, Cui
H
, Wang
L
, Luo
X
, et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1
. J Immunol
. 2010
;184
(12
):6773
–81
. 20.
Gonzalez-Martin
A
, Adams
BD
, Lai
M
, Shepherd
J
, Salvador-Bernaldez
M
, Salvador
JM
, et al. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity
. Nat Immunol
. 2016
;17
(4
):433
–40
. 21.
Zhu
A
, Xia
J
, Zuo
J
, Jin
S
, Zhou
H
, Yao
L
, et al. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer
. Med Oncol
. 2012
;29
(4
):2701
–9
. 22.
Meinzinger
J
, Jäck
HM
, Pracht
K
. miRNA meets plasma cells “How tiny RNAs control antibody responses”
. Clin Immunol
. 2018
;186
:3
–8
. 23.
Schanen
BC
, Li
X
. Transcriptional regulation of mammalian miRNA genes
. Genomics
. 2011
;97
(1
):1
–6
. 24.
Xu
X
, Fan
Z
, Kang
L
, Han
J
, Jiang
C
, Zheng
X
, et al. Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis
. J Clin Investig
. 2013
;123
(2
):630
–45
. 25.
Sakamoto
N
, Naito
Y
, Oue
N
, Sentani
K
, Uraoka
N
, Oo
HZ
, et al. MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis
. Cancer Sci
. 2014
;105
(2
):236
–43
. 26.
Liffers
ST
, Munding
JB
, Vogt
M
, Kuhlmann
JD
, Verdoodt
B
, Nambiar
S
, et al. MicroRNA-148a is down-regulated in human pancreatic ductal adenocarcinomas and regulates cell survival by targeting CDC25B
. Lab Invest
. 2011
;91
(10
):1472
–9
. 27.
Patel
JB
, Appaiah
HN
, Burnett
RM
, Bhat-Nakshatri
P
, Wang
G
, Mehta
R
, et al. Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22
. Oncogene
. 2011
;30
(11
):1290
–301
. 28.
Xu
Q
, Liu
LZ
, Yin
Y
, He
J
, Li
Q
, Qian
X
, et al. Regulatory circuit of PKM2/NF-κB/miR-148a/152-modulated tumor angiogenesis and cancer progression
. Oncogene
. 2015
;34
(43
):5482
–93
. 29.
Zhao
M
, Su
Z
, Zhang
S
, Zhuang
L
, Xie
Y
, Li
X
. Suppressive role of MicroRNA-148a in cell proliferation and invasion in ovarian cancer through targeting transforming growth factor-β-induced 2
. Oncol Res
. 2016
;24
(5
):353
–60
. 30.
Chen
Q
, Wang
Y
, Dang
H
, Wu
X
. MicroRNA-148a-3p inhibits the proliferation of cervical cancer cells by regulating the expression levels of DNMT1 and UTF1
. Oncol Lett
. 2021
;22
(2
):617
. 31.
Zhang
BX
, Yu
T
, Yu
Z
, Yang
XG
. MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9
. Eur Rev Med Pharmacol Sci
. 2019
;23
(15
):6497
–504
. 32.
Luo
Q
, Li
W
, Zhao
T
, Tian
X
, Liu
Y
, Zhang
X
. Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway
. Arch Biochem Biophys
. 2015
;583
:47
–54
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