Abstract
Introduction: Cervical cancer is one of the most common malignant tumors among women in the world. MicroRNA-449a (miR-449a) has been identified as a tumor suppressor gene in various cancers. Our present study aimed to explore the biological role of miR-449a in cervical cancer. Methods: The expression of miR-449a in cervical cancer tissues and cell lines was detected using real-time quantitative PCR. Kaplan-Meier survival analysis and a Cox regression assay were used to identify the prognostic significance of miR-449a in cervical cancer. A CCK-8 assay and a Transwell assay were performed to determine the impact of miR-449a on the proliferation, migration, and invasion of cervical cancer cells. Results: The expression of miR-449a was decreased in both cervical cancer tissues and cell lines. The decreased expression of miR-449a was significantly associated with lymph node metastasis, differentiation, and FIGO stage, as well as with poor survival. In vitro, transfection of miR-449a mimic into cervical cancer cells inhibited cell proliferation, migration, and invasion. Conclusion: All of the results revealed that miR-449a functions as a suppressor gene and inhibits cell proliferation, migration, and invasion in cervical cancer. In addition, it may serve as a prognostic biomarker for cervical cancer.
Journal Section:
Research Article
References
1.
Daniyal
M
, Akhtar
N
, Ahmad
S
, Fatima
U
, Akram
M
, Asif
HM
. Update knowledge on cervical cancer incidence and prevalence in Asia
. Asian Pac J Cancer Prev
. 2015
;16
(9
):3617
–20
.
[PubMed]
1513-73682.
Ouh
YT
, Lee
JK
. Proposal for cervical cancer screening in the era of HPV vaccination
. Obstet Gynecol Sci
. 2018
May
;61
(3
):298
–308
.
[PubMed]
2287-85723.
Landy
R
, Pesola
F
, Castañón
A
, Sasieni
P
. Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case-control study
. Br J Cancer
. 2016
Oct
;115
(9
):1140
–6
.
[PubMed]
0007-09204.
Wei
M
, Zhou
W
, Bi
Y
, et al.. Rising Mortality Rate of Cervical Cancer in Younger Women in Urban China
. J Gen Intern Med
. 2018
.
[PubMed]
0884-87345.
Pelkofski E, Stine J, Wages NA, Gehrig PA, Kim KH, Cantrell LA. Cervical Cancer in Women Aged 35 Years and Younger. Clin Ther. 2016 Mar;38(3):459–66.
6.
Lee
S
, Vasudevan
S
. Post-transcriptional stimulation of gene expression by microRNAs
. Adv Exp Med Biol
. 2013
;768
:97
–126
.
[PubMed]
0065-25987.
Bartel
DP
. MicroRNAs: target recognition and regulatory functions
. Cell
. 2009
Jan
;136
(2
):215
–33
.
[PubMed]
0092-86748.
Zhang
Q
, Zhang
K
, Zhang
C
, Ge
H
, Yin
Y
, Feng
H
, et al.. MicroRNAs as Big Regulators of Neural Stem/Progenitor Cell Proliferation, Differentiation and Migration: A Potential Treatment for Stroke
. Curr Pharm Des
. 2017
;23
(15
):2252
–7
.
[PubMed]
1381-61289.
Liu
H
, Cao
B
, Zhao
Y
, Liang
H
, Liu
X
. Upregulated miR-221/222 promotes cell proliferation and invasion and is associated with invasive features in retinoblastoma
. Cancer Biomark
. 2018
;22
(4
):621
–9
.
[PubMed]
1574-015310.
Zhou
M
, Chen
X
, Wu
J
, He
X
, Ren
R
. MicroRNA-143 regulates cell migration and invasion by targeting GOLM1 in cervical cancer
. Oncol Lett
. 2018
Nov
;16
(5
):6393
–400
.
[PubMed]
1792-107411.
Cheng
J
, Wu
LM
, Deng
XS
, Wu
J
, Lv
Z
, Zhao
HF
, et al.. MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway
. Hepatobiliary Pancreat Dis Int
. 2018
Aug
;17
(4
):336
–44
.
[PubMed]
1499-387212.
Jiang
T
, Liu
J
, Mu
J
. Downregulation of microRNA‑449a‑5p promotes esophageal squamous cell carcinoma cell proliferation via cyclin D1 regulation
. Mol Med Rep
. 2018
Jul
;18
(1
):848
–54
.
[PubMed]
1791-299713.
Li
F
, Liang
J
, Bai
L
. MicroRNA-449a functions as a tumor suppressor in pancreatic cancer by the epigenetic regulation of ATDC expression
. Biomed Pharmacother
. 2018
Jul
;103
:782
–9
.
[PubMed]
0753-332214.
Ye
W
, Xue
J
, Zhang
Q
, Li
F
, Zhang
W
, Chen
H
, et al.. MiR-449a functions as a tumor suppressor in endometrial cancer by targeting CDC25A
. Oncol Rep
. 2014
Sep
;32
(3
):1193
–9
.
[PubMed]
1021-335X15.
Zhang
Q
, He
XJ
, Ma
LP
, Li
N
, Yang
J
, Cheng
YX
, et al.. [Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues]
. Zhonghua Zhong Liu Za Zhi
. 2011
Dec
;33
(12
):885
–90
.
[PubMed]
0253-376616.
Wakatsuki
M
, Kato
S
, Kiyohara
H
, Ohno
T
, Karasawa
K
, Tamaki
T
, et al.. The prognostic value of rectal invasion for stage IVA uterine cervical cancer treated with radiation therapy
. BMC Cancer
. 2016
Mar
;16
(1
):244
.
[PubMed]
1471-240717.
Vural
C
, Bayrak
BY
, Muezzınoglu
B
, Yucesoy
I
. Perineural invasion is a valuable prognostic factor in advanced stage and/or Node (+) cervical cancer
. Indian J Pathol Microbiol
. 2017
Jan-Mar
;60
(1
):27
–32
.
[PubMed]
0974-513018.
Kumar
L
, Harish
P
, Malik
PS
, Khurana
S
. Chemotherapy and targeted therapy in the management of cervical cancer
. Curr Probl Cancer
. 2018
Mar - Apr
;42
(2
):120
–8
.
[PubMed]
0147-027219.
Dan
B
, Luo
J
, Li
K
, Chen
S
. Prognostic Value of miR-375 for Survival Outcomes in Various Cancers: A Systematic Review and Meta-Analysis
. Oncol Res Treat
. 2018
;41
(1-2
):47
–50
.
[PubMed]
2296-527020.
Lei
Y
, Liu
Z
, Yang
W
. Negative correlation of cytoplasm TIMP3 with miR-222 indicates a good prognosis for NSCLC
. OncoTargets Ther
. 2018
Sep
;11
:5551
–7
.
[PubMed]
1178-693021.
Feng
R
, Sah
BK
, Li
J
, Lu
S
, Yuan
F
, Jin
X
, et al.. miR-126: an indicator of poor prognosis and recurrence in histologically lymph node-negative gastric cancer
. Cancer Biomark
. 2018
;23
(3
):437
–45
.
[PubMed]
1574-015322.
Sun
D
, Lu
J
, Hu
C
, Zhang
Q
, Wang
X
, Zhang
Z
, et al.. Prognostic role of miR-760 in hepatocellular carcinoma
. Oncol Lett
. 2018
Dec
;16
(6
):7239
–44
.
[PubMed]
1792-107423.
Zhang Q, Lv R, Guo W, Li X. microRNA-802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine-rich splicing factor 9. J Cell Biochem. 2019 Jun;120(6):10370–9.
24.
Zhang
Q
, Lv
R
, Guo
W
, et al.. microRNA-802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine-rich splicing factor 9
. J Cell Biochem
. 2018
.
[PubMed]
0730-231225.
Park
S
, Eom
K
, Kim
J
, Bang
H
, Wang
HY
, Ahn
S
, et al.. MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer
. BMC Cancer
. 2017
Sep
;17
(1
):658
.
[PubMed]
1471-240726.
Cui
J
, Pan
Y
, Wang
J
, Liu
Y
, Wang
H
, Li
H
. MicroRNA-206 suppresses proliferation and predicts poor prognosis of HR-HPV-positive cervical cancer cells by targeting G6PD
. Oncol Lett
. 2018
Nov
;16
(5
):5946
–52
.
[PubMed]
1792-107427.
Zamani S, Sohrabi A, Hosseini SM, Rahnamaye-Farzami M, Akbari A. Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection. Microrna. 2019;8(2):110–5.
28.
Wu D, Liu J, Chen J, et al. MiR-449a suppresses tumor growth, migration and invasion in non-small cell lung cancer by targeting HMGB1-mediated NF-κB signaling way. Oncol Res. 2019 Feb;27(2):227–35.
29.
Zamani
S
, Sohrabi
A
, Hosseini
SM
, et al.. Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection
. MicroRNA
. 2018
.
[PubMed]
2211-536630.
Hu
Y
, Wu
AY
, Xu
C
, Song
KQ
, Wang
WJ
, Yin
X
, et al.. MicroRNA-449a Inhibits Tumor Metastasis through AKT/ERK1/2 Inactivation by Targeting Steroid Receptor Coactivator (SRC) in Endometrial Cancer
. J Cancer
. 2019
Jan
;10
(2
):547
–55
.
[PubMed]
0378-236031.
Ishikawa
D
, Takasu
C
, Kashihara
H
, Nishi
M
, Tokunaga
T
, Higashijima
J
, et al.. The Significance of MicroRNA-449a and Its Potential Target HDAC1 in Patients With Colorectal Cancer
. Anticancer Res
. 2019
Jun
;39
(6
):2855
–60
.
[PubMed]
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