ISSN 0026-8933, Molecular Biology, 2017, Vol. 51, No. 4, pp. 555–561. © Pleiades Publishing, Inc., 2017.
Published in Russian in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 4, pp. 629–636.
miR-218 Promoted the Apoptosis of Human Ovarian Carcinoma
Cells via Suppression of the WNT/β-Catenin Signaling Pathway
, S.-H. Liang
, L.-B. Xiang
, X.-T. Han
, W. Zhang
, X.-H. Wu
, and M.-Q. Zhang
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
Received July 5, 2016; in final form, September 8, 2016
Abstract⎯MicroRNA-218 (miR-218) is a short, noncoding RNA, with multiple biological functions. In this
study, we aimed to investigate the potential effects of miR-218 on the apoptosis of human ovarian carcinoma
cells and the underlying mechanisms by which miR-218 exerted its actions. After over-expressing miR-218 in
human ovarian carcinoma (OVCAR3) cells, cell viability was determined by MTT method, cell apoptosis was
observed by f low cytometry (FCM), mRNA expression of miR-218, Bcl2, Bax was measured by RT-PCR and
protein expression levels of Wnt, tankyrase and β-catenin were quantified by Western blots. Over-expression
of miR-218 potently suppressed cell viability and promoted the apoptosis of human ovarian carcinoma cells
in a time-dependent manner. In addition, the down-regulation of tankyrase expression level was detected in
miR-218-over-expressed cells. Following the block of the Wnt/β-catenin signaling pathway using the inhib-
itor XAV-939, the effects of miR-218 on the proliferation and apoptosis of human ovarian carcinoma cells
were significantly suppressed. Augmenting expression of miR-218 and/or miRNA-218 mimicking therapeu-
tics may provide viable avenue for the treatment of ovarian cancer.
Keywords: miR-218, human ovarian carcinoma cells, proliferation, apoptosis, Wnt/β-catenin
Ovarian cancer accounts for about 3% of cancers
among women, being the second leading cause of
death among patients with gynecologic cancers .
Worldwide, newly diagnosed cases of ovarian cancer
have reached 238719; high mortality rate for ovarian
cancer persists with 151917 deaths per year . Surgi-
cal and chemotherapeutical treatments for ovarian
cancer have enhanced the survival rates . However,
the prognosis of patients at late-stage is still poor .
Therefore, the molecular pathology of ovarian cancer
has to be studied in greater details.
MicroRNAs (miRNAs), a class of short, non-cod-
ing RNA molecules with important biological and
pathological functions, are known to play regulatory
roles during cancer metastasis . Additionally, miR-
NAs are being mined for novel biomarkers allowing
the detection of cancers . Notably, previous studies
have revealed that miR-218 can act as a tumor sup-
pressor as it inhibits both invasion and proliferation of
cancer cells by down-regulating the expression of mul-
tiple target genes . For instance, miR-218 can sup-
press nasopharyngeal cancer progression through
down-regulation of BIRC5 (survivin) and the SLIT2
(slit guidance ligand 2)-ROBO1 (roundabout guid-
ance receptor 1) pathway . In oral cancers, miR-218
had been shown to target mTOR component RICTOR
(Rictor) . Furthermore, miR-218 is a negative reg-
ulator of osteoclastogenesis and bone resorption as it
exerts its action by suppressing the p38MAPK-c-Fos-
NFATc1 pathway .
The Wnt/β-catenin is a genetically conserved sig-
naling pathway responsible for several cellular pro-
cesses, including cell proliferation, apoptosis and dif-
ferentiation [11‒13]. Abnormal activation of the
Wnt/β-catenin signaling pathway is closely related to
the development of a variety of cancers [14, 15].
Here, we evaluated the effects of miR-128 on the
proliferation and apoptosis of human ovarian carcinoma
cells, and the relationship between miR-128 overexpres-
sion and the Wnt/β-catenin signaling pathway.
Cell culture. OVCAR-3 human ovarian carcinoma
cells were purchased from the Cell Bank of Type Cul-
ture Collection of the Chinese Academy of Sciences
(Shanghai, China). Cells were cultured in complete
The article is published in the original.
MOLECULAR CELL BIOLOGY