ORIGINAL PAPER
LncRNA UCA1-miR-507-FOXM1 axis is involved in cellproliferation, invasion and G0/G1 cell cycle arrest in melanoma
Yanping Wei1 • Qianqian Sun2 • Lindong Zhao1 • Jianbo Wu2 • Xiaonan Chen2 •
Yuanyuan Wang2 • Wenqiao Zang2 • Guoqiang Zhao2,3
Received: 4 May 2016 / Accepted: 1 July 2016 / Published online: 7 July 2016
� Springer Science+Business Media New York 2016
Abstract Recently, the incidence of melanoma has been
on the rise. Patients with distant metastasis share poor
prognosis. Increasing studies have been conducted to
clarify the molecular mechanisms as well as to investigate
potential effective therapeutic targets in the development of
melanoma. This study focuses on the LncRNA UCA1 and
its downstream regulated factors. In our experiments,
UCA1 expression was discovered to be upregulated in
melanoma tissues and cells, while the depletion of UCA1
led to the inhibition of cell proliferation, invasion and cell
cycle arrest. To further our understanding of the mecha-
nisms of UCA1, a system of experiments was built. We
found that miR-507 could directly bind to UCA1 at the
miRNA recognition site, and that there was a negative
correlation between miR-507 and UCA1. Additionally,
FOXM1 is a target of miR-507 and can be downregulated
by either miR-507 overexpression or UCA1 depletion.
Downregulated FOXM1 was analogous to the depletion of
UCA1 and the overexpression of miR-507. These results,
taken together, provide evidence for a novel UCA1 inter-
action regulatory network in tumorigenesis of melanoma.
Keywords Melanoma � LncRNA UCA1 � miR-507 �FOXM1
Introduction
Melanoma is a deadly malignancy if not caught early, and
its incidence has increased more rapidly than that of any
other type of cancer worldwide [1]. According to recent
estimates, melanoma will likely surpass colorectal cancer
to become the fifth most common type of cancer by 2030
[2]. Despite the fact that numerous treatments exist, the
most effective treatment method still relies heavily on early
diagnosis and surgical resection. People with distant
metastasis receive poor prognosis, with a 5-year survival
rate of only 16 % [3]. Melanoma formation is the result of
multiple factors involving many kinds of oncogene acti-
vation and anti-oncogene inactivation. Nowadays, a
growing number of studies have been focusing on resolving
the molecular mechanisms as well as on investigating the
effective therapeutic targets in the development of
melanoma.
Long non-coding RNAs (lncRNAs) are defined as non-
coding transcripts with over 200 nucleotides in length and
have been reported to play important roles in modulating
tumor genesis and progression [4–6]. Tian Y et al. have
explored the roles of abnormally expressed long non-cod-
ing RNA UCA1 and Malat-1 in metastasis of melanoma
and have discovered a possible correlation between the
increased expression of UCA1 and of Malat-1 lncRNAs
with melanoma metastasis [7]. However, the specific
molecular mechanisms remain to be further investigated.
miR-507 has been defined as a tumor suppressor for its
inhibitory effects in many cancer cells, including cervical
cancer, esophageal cancer, lung cancer and liver cancer [8].
Yanping Wei and Qianqian Sun have contributed equally to this work.
& Guoqiang Zhao
1 Department of Dermatology, The People’s Hospital of
Jiaozuo City, Jiaozuo 454000, Henan, China
2 School of Basic Medical Sciences, Zhengzhou University,
Zhengzhou 450001, Henan, China
3 Collaborative Innovation Center of Cancer
Chemoprevention, Zhengzhou 450001, Henan, China
123
Med Oncol (2016) 33:88
DOI 10.1007/s12032-016-0804-2
Schmitt AM et al. declared that lncRNAs drived many
important cancer phenotypes through their interactions
with other cellular macromolecules including DNA, pro-
tein and RNA [9]. UCA1 has been reported to promote
colorectal cancer via inhibiting miR-204-5p [10]. The pre-
experiment and bioinformatics analysis demonstrated that
miR-507 contained complementary binding sites for
lncRNA UCA1. Based on this finding, whether UCA1 and
miR-507 may closely interact in the regulation of mela-
noma is a topic that requires additional extensive research.
In our current research, we discovered a novel mecha-
nism through which UCA1 regulated miR-507. Addition-
ally, FOXM1 was verified as a new target of miR-507 in
regulating growth and invasion of melanoma.
Materials and methods
Clinical sample collection
After investigated by Ethics Committee of Life Sciences of
Zhengzhou University, the research content had been
confirmed to follow the requirements of the ethical stan-
dards about life sciences approved by International and
Chinese Ethics Committee. All patients were informed
about the aims of specimen collection and had signed
written consent. The tissues were collected during surgery
performed at the First Affiliated Hospital of Zhengzhou
University and People’s Hospital of Jiao Zuo, between
February 2013 and February 2015. Primary cutaneous
malignant melanoma tissues were obtained from 18
patients. And metastatic melanoma tissues were collected
from 19 patients. A total of 20 benign nevi obtained from
20 patients were defined as normal controls.
Cell culture
Human melanoma cell lines (A375 and SK-MEL-2) were
purchased from the Cell Bank of the Chinese Academy of
Sciences (Shanghai, China). Cells were cultured in DMEM
medium supplemented with 20 % fetal bovine serum (FBS)
in a 5 % CO2 atmosphere at 37 �C.
Cell transfection
Cells were seeded into six-well plates at a density of
5 9 104 cells/wells to reach about 50–80 % confluence for
transfection. siRNAs of UCA1 (si-UCA1) were designed
and synthesized by GenePharma (Shanghai, China). Tran-
sient transfection was conducted by LipofectamineTM 2000
(Invitrogen, Carlsbad, CA) following the manufactures’
instructions. Cells from each line were separated into five
groups: The si-UCA1 group was transfected with si-UCA1,
the miR-507 group was transfected with miR-507 mimics,
the co-transfection group (si-UCA1 ? miR-507) was
transfected with si-UCA1 and miR-507 mimics, the NC
group was transfected with scrambled oligonucleotide, and
the Blank group was not transfected. The transfected effi-
ciencies were examined by quantitative real-time PCR
(qRT-PCR).
RNA and miRNA extraction and quantitative RT-
PCR
Total RNA was extracted from the melanoma tissues and
A375 and SK-MEL-2 cells using Trizol reagent (Life
Technologies Corporation, Carlsbad, CA, USA). Reaction
mixture (20 ll) containing 1–3 lg of total RNA was
reversely transcribed to cDNA by using PrimeScript RT-
polymerase (Takara, Dalian, China). The quantitative PCR
was performed on the cDNA with specific primers for
UCA1 and FOXM1; the GAPDH was served as an internal
control. The stem-loop reverse transcriptase polymerase
chain reaction (RT-PCR) for miR-507 was measured with
the control of U6. And qRT-PCR was applied using the
ABI power SYBR� Green PCR Master Mix (Applied
Biosystems, Foster City, CA, USA). All process was per-
formed according to the manufactures’ instructions.
Cell proliferation assay
According to the manufacturers’ instructions, cell viability
was assessed using the Cell Counting Kit 8 (CCK-8;
Dojindo Molecular Technologies, Rockville, MD, USA) to
confirm whether the downregulation of si-UCA1 and
upregulation of miR-507 contributed to the inhibition of
cell proliferation. Cells were cultured into a 96-well plate
at a density of 0.5 9 104 cells/well at 37 �C, and the cell
viability was measured for different times (0 h, 24 h, 48 h
and 72 h) by a microplate reader (Model 680; Bio-Rad
Laboratories, Hercules, CA, USA) by spectrophotometry at
450 nm.
Invasion assay
Cell invasion assay was performed using the Transwell
insert chamber coated with Matrigel (BD Biosciences). The
transfected cells were resuspended in a 100-lL serum-free
medium at a density of 1 9 105 cells/mL and were added
to the upper chamber. The lower chamber was supplied
with 500 lL of DMEM/high-glucose or DMEM/F12
medium supplemented with 10 % FBS. After 24-h incu-
bation in a cell incubator at 37 �C, the cells on the top
surface of the insert were removed. Cells that had invaded
to the lower side of the membrane were fixed with
methanol and stained with 20 % Giemsa. The number of
88 Page 2 of 9 Med Oncol (2016) 33:88
123
cells was counted in five randomly chosen fields, and the
average number was calculated. Each test was performed in
triplicate.
Cell cycle analysis
The flow cytometry assay was performed to assess the cell
cycle distribution. 48 h after the cells transfection, cells
were stained with 20 lg/mL PI (Sigma-Aldrich, St Louis,
MO, USA) and 100 lg/mL RNase A in PBS for 15 min at
room temperature. A FACScan flow cytometer (BD Bio-
sciences, San Jose, CA) was used for the analysis.
Bioinformatics prediction and luciferase reporter
assay
A web-based program known as miRcode and the Tar-
getScan program were used to predict the target genes of
UCA1 and miR-507 and their conserved sites that match
the seed region. To construct the luciferase reporter vec-
tors, the entire UCA1 sequence (wild-type) was inserted
into the downstream of the pmirGLO promoter vector
(Promega, Madison, WI) and assigned as WT LncRNA
UCA1. The MT LncRNA UCA1 without the miR-507
binding sites was generated using QuikChange Multi Site-
Directed Mutagenesis kit (Stratagene, LaJolla, CA, USA).
The wild-type 30UTR of FOXM1 mRNA containing the
presumed target region for miR-507 was amplified by PCR.
The mutagenesis of the seed region was conducted with a
mutant primer. The WT FOXM1 30UTR and MT FOXM1
30UTR fragments were, respectively, inserted into the
pmirGLO promoter vector (Promega, Madison, WI)
downstream of the luciferase gene to generate recombinant
plasmids. When it comes to the luciferase reporter assay,
the cells were co-transfected using the LipofectamineTM
2000 (Invitrogen, Carlsbad, CA) according to the manu-
facturers’ instructions with miR-507 mimics and scrambled
oligonucleotide. After being treated for 24 h, the luciferase
activities were measured using the dual-luciferase reporter
assay system (Promega, Madison, WI, USA) according to
manufactures’ instructions.
RNA immunoprecipitation
A375 and SK-MEL-2 cells were lysed using a complete
RNA lysis buffer containing protease inhibitor and RNase
inhibitor using an EZ-Magna RIP RNA-binding protein
immunoprecipitation kit (Millipore, Billerica, MA, USA)
following the manufacturers’ instructions. 100 lL of whole
cell lysate was incubated with the RIP immunoprecipita-
tion buffer containing magnetic beads coated with human
anti-Argonaute 2 (Ago2) antibody (Millipore) and was
designated as the test group, while the control group
(Millipore) consisted of normal mouse IgG. After being
incubated for 2 h at 4 �C, the immunoprecipitated RNA
was isolated. The RNA concentration was measured by a
NanoDrop (Thermo Scientific), and the RNA quality was
determined using a bioanalyzer (Agilent, Santa Clara, CA,
USA). Next, the purified RNA was further used in the qRT-
PCR analysis of UCA1 and miR-507.
Western blotting
After 24-h transfection, total protein (50 lg) was extractedfrom the A375 and SK-MEL-2 cells using the RIPA buffer,
and the BCA Protein Assay Kit (Beyotime, China) was
then used to assess the protein concentrations. The sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-
PAGE) was performed to separate the objective protein
from the total protein. Polyvinylidene difluoride mem-
branes were used to be transferred. After being blocked in
5 % skim milk for 2 h and being washed four times with
TBST at room temperature, the membranes were incubated
with the primary antibody (polyclonal rabbit anti-human
FOXM1 antibody, Santa Cruz Biotechnology, Santa Cruz,
CA) overnight at 4 �C. Following four washes with TBST,
the membranes were incubated with the primary antibody
(horseradish peroxidase-conjugated goat anti-rabbit IgG,
Santa Cruz Biotechnology) for 2 h. A chemiluminescence
detection kit (Amersham Pharmacia Biotech, Piscataway,
NJ) was used to visualize all blots. The antibody against
GAPDH was used as control.
Statistical analysis
The data obtained from our experiments were presented as
mean ± standard deviation (SD) and analyzed using vari-
ance (ANOVA) test, student’s t test and Linear Regression
test that were a part of the SPSS software (version 21.0).
The qRT-PCR results were analyzed using the 2-DDCt
method. P\ 0.05 was considered statistically significant.
Results
LncRNA UCA1 and FOXM1 mRNA are
significantly upregulated in melanoma tumor tissues
The samples obtained from metastatic melanoma, primary
melanoma, melanocytic nevi, A375, and SK-MEL-2 cell
lines were examined to detect the expression of LncRNA
UCA1 and FOXM1 mRNA with the help of RT-PCR.
Compared with the melanocytic nevi tissues, upregulated
expression of UCA1 and FOXM1 mRNA was observed in
the metastatic melanoma and the primary melanoma tis-
sues, as well as in the A375 and SK-MEL-2 cell lines.
Med Oncol (2016) 33:88 Page 3 of 9 88
123
Besides, UCA1 and FOXM1 mRNA expressions were
significantly elevated in tissues without metastasis than in
tissues from patients without metastasis (P\ 0.05; Fig. 1a,
b). After statistical analysis of these data, the expression of
UCA1 and FOXM1 mRNA were found to be positively
related (R2 = 0.613, P\ 0.05; Fig. 1c).
Above all, UCA1 and FOXM1 expression was clearly
upregulated in the melanoma tumor tissues, and the
expression of UCA1 correlates positively with that of
FOXM1.
LncRNA UCA1 depletion suppresses cell
proliferation and invasion and induces cell cycle
arrest in A375 and SK-MEL-2 cell lines
Based on the above observations, UCA1 was found to be
upregulated in melanoma tumor tissues as well as in A375
and SK-MEL-2 cell lines. Then, we concentrated our
examination on the effect of UCA1 in melanoma cells. We
constructed a scrambled UCA1 and a siRNA-mediated
UCA1 depletion and transfected them separately into A375
and SK-MEL-2 cell lines. Successful transfection was
confirmed using qRT-PCR (Fig. 2a). CCK-8 assay was
used to evaluate the cell proliferation. After being cultured
for three days, cells transfected with si-UCA1 visibly
exhibited the lowest proliferation among the control groups
(P\ 0.05; Fig. 2b, c). The transwell assay was used to
detect the effect of UCA1 depletion on cell invasion. The
number of invasive cells decreased dramatically in cells
transfected with si-UCA1 (P\ 0.05; Fig. 2d). A cell cycle
analysis was conducted on the cells above using flow
cytometry. As a result, we found that the cells in the si-
UCA1 group had an arrested cell cycle with a lower pro-
portion of S-phase and G2/M-phase cells and a higher
proportion of G0/G1-phase cells, when compared to the
control groups (P\ 0.05; Fig. 2e). Taken together, it can
be reasonably concluded that the depletion of LncRNA
UCA1 depletion could suppress cell proliferation and cell
invasion and could also induce a G0/G1 cell cycle arrest in
A375 and SK-MEL-2 cell lines.
LncRNA UCA1 directly interacts with miR-507
in A375 and SK-MEL-2 cells
Numerous recent studies reported that lncRNAs has
sequence complementary to miRNAs that could potentially
have an inhibitory effect on miRNAs’ expression and
activity [11]. We then conducted a series of experiments in
order to examine whether UCA1 has an inhibitory effect on
miRNAs in melanoma cells. The miRcode program was
used and allowed us to observe the putative binding sites
between UCA1 and miR-507 (Fig. 3a). The level of miR-
507 and UCA1 were measured in the melanoma tissues by
qRT-PCR; the data obtained showed an inverse relation-
ship between them (R2 = 0.578, P\ 0.05; Fig. 3b). Fig-
ure 3c indicates that the depletion of UCA1 significantly
upregulated the expression level of miR-507 in A375 and
SK-MEL-2 cell lines (P\ 0.05). On the contrary, Fig. 3d
demonstrates that the overexpression of miR-507 notice-
ably inhibited the expression of UCA1 (P\ 0.05). More-
over, the luciferase reporter assay was conducted in order
to gain more insights into the relationship between UCA1
and miR-507 and revealed that while miR-507 repressed
the luciferase activity of WT LncRNA UCA1 (P\ 0.05;
Fig. 1 Expressions of LncRNA UCA1, FOXM1 in melanoma tumor
issues and cells as determined by quantitative real-time PCR (qRT-
PCR). a, b Relative expression levels of LncRNA UCA1 and FOXM1
in tissues of metastatic melanoma, primary melanoma and melano-
cytic nevi, as well as in A375 and SK-MEL-2 cell lines. c Linear
regression analysis of LncRNA UCA1 and FOXM1 expression in
tumor tissues from metastatic melanoma patients. *P\ 0.05
88 Page 4 of 9 Med Oncol (2016) 33:88
123
Fig. 3e), it did not affect the MT LncRNA UCA1 lucifer-
ase activity (P[ 0.05). In summary, it can be concluded
that miR-507 could directly bind to UCA1 at the miRNA
recognition site, and that there was a negative correlation
between miR-507 and UCA1. To more extensively analyze
the mechanism that might be involved in the reciprocal
relationship, RNA immunoprecipitation experiments were
taken using antibody against Ago2, a key component of
RISC complex. The results of our experiment indicated that
both miR-507 and UCA1 were in the Ago2-pulled down
pellet (Fig. 3f, g).
FOXM1 is a target of miR-507, and downregulated
FOXM1 plays a role in suppressing cell proliferation
and invasion and inducing cell cycle arrest in A375
and SK-MEL-2 cell lines
The overexpression of FOXM1 was examined in the mel-
anoma tissues and cell lines in earlier experiments. In
addition, TargetScan and miRanda prediction algorithms
showed that the FOXM1 might be targeted by miR-507
(Fig. 4a). A dual-luciferase reporter assay was performed,
with the results shown in Fig. 4b; from these results, we
were able to confirm what we had previously predicted.
Next, in order to explore the relationship among FOXM1,
UCA1 and miR-507, the A375 and SK-MEL-2 cells were
transfected with si-UCA1, miR-507 mimics, and a
combination of si-UCA1 and miR-507 mimics, while the
control cells were transfected with nothing. Western blot-
ting was performed in order to detect the protein expression
level of FOXM1; qPCR was used to evaluate the expres-
sion of FOXM1 mRNA. Compared with the control
groups, FOXM1 mRNA was significantly reduced in the si-
UCA1, miR-507 mimics and the combination of si-
UCA1and miR-507 mimics groups (P\ 0.05; Fig. 4c), the
protein expression exhibited the same trend (P\ 0.05;
Fig. 4d). Besides, the combination of si-UCA1 and miR-
507 mimics group had a distinctly higher expression level
than the si-UCA1 group (P\ 0.05) and the miR-507
mimics group (P\ 0.05). The behavior of the cells from
each of the five groups was examined by a CCK-8 assay, a
transwell assay and a flow cytometry. The outcomes of
these experiments and assays demonstrate that the down-
regulated UCA1 and the upregulated miR-507 could
reduce cell proliferation (P\ 0.05; Fig. 4e) and invasion
(P\ 0.05; Fig. 4f) and could also induce G0/G1 cell cycle
arrest (P\ 0.05; Fig. 4g). Furthermore, the group that
consisted of cells transfected with a combination of si-
UCA1 and miR-507 mimics showed a more profound
inhibitory effect than the other two groups (P\ 0.05).
To sum up, FOXM1 is a target of miR-507, and can be
downregulated by either miR-507 overexpression or UCA1
depletion. The results obtained from these in vitro experi-
ments suggest the existence of a UCA1-miR-507-FOXM1
Fig. 2 LncRNA UCA1 depletion suppresses cell proliferation and
invasion and induces cell cycle arrest in A375 and SK-MEL-2 cell
lines. a UCA1 expression levels were evaluated using qRT-PCR in si-
UCA1-transfected A375 and SK-MEL-2 cells. b, c cell proliferation
were detected in UCA1 downregulated cells using CCK-8 assay.
d transwell assay was performed in UCA1 downregulated cells to
investigate changes in cell invasiveness. e the cell cycle analysis wasdetected by flow cytometry. *P\ 0.05
Med Oncol (2016) 33:88 Page 5 of 9 88
123
coupling that could inhibit cell proliferation and cell
invasion, as well as induce a G0/G1 cell cycle arrest in
A375 and SK-MEL-2 cell lines.
Discussion
UCA1 has been reported as an oncogene and has been
found to be upregulated in various kinds of tumors [12].
For example, in non-small cell lung cancer, UCA1 func-
tions as an oncogene, acting mechanistically by upregu-
lating ERBB4 in part through ‘spongeing’ miR-193a-3p
[13]. UCA1 sustains proliferation of AML cells by
repressing the expression of the cell cycle regulator
p27kip1 [14]. In our experiments, UCA1 was verified to be
upregulated in melanoma tumor tissues and A375 and SK-
MEL-2 cell lines. Moreover, we discovered that UCA1
depletion could suppress cell proliferation and invasion and
could also induce G0/G1 cell cycle arrest in A375 and SK-
MEL-2 cell lines. The mechanisms that are involved in the
biological functions of UCA1 require more extensive
research.
Over the past several years, competing endogenous
RNAs (ceRNAs) have emerged as an important class of
post-transcriptional regulators that alter gene expression
through a miRNA-mediated mechanism [15]. Based on the
previous studies concerning the regulation of miRNA by
UCA1 [10, 16], we further explored the role and
Fig. 3 LncRNA UCA1 directly interacts with miR-507 in A375 and
SK-MEL-2 cells. a Predicted binding sites between UCA1 and miR-
507. b Linear regression analysis of LncRNA UCA1 and miR-507
expression in tumor tissues from metastatic melanoma patients.
c miR-507 levels were detected by qRT-PCR in A375 and SK-MEL-2
cells transfected with si-UCA1. d UCA1 levels were detected by
qRT-PCR in A375 and SK-MEL-2 cells transfected with miR-507
mimics. e The relative luciferase activities were inhibited in the A375
and SK-MEL-2 cells transfected with the reporter vector WT
LncRNA UCA1, not with the reporter vector MT LncRNA UCA1.
Association of miR-507 (f) and UCA1 (g) with Ago2 in A375 and
SK-MEL-2 cells. Cellular lysates from A375 and SK-MEL-2 cells
were used for RNA immunoprecipitation with antibody against Ago2.
UCA1 and miR-507 expression levels were detected using qRT-PCR.
Data were presented as mean ± SD from three independent exper-
iments. *P\ 0.05
88 Page 6 of 9 Med Oncol (2016) 33:88
123
mechanisms in which UCA1 exerts oncogenic functions by
targeting miRNAs. Bioinformatics analysis presented the
complementary binding sites between UCA1 and miR-507.
And the data obtained from melanoma tissues showed an
inverse expression trend between them. In the A375 and
SK-MEL-2 cell lines, knockdown of UCA1 (si-UCA1)
increased the expression of miR-507, while ectopic
expression of miR-507 decreased UCA1 expression. The
luciferase reporter assay was conducted to reveal that miR-
507 might be the target of UCA1; RNA immunoprecipi-
tation experiments were taken to show that miR-507 could
directly bind to UCA1 at the miRNA recognition site.
Therefore, we could confirm that there was a negative
correlation between miR-507 and UCA1.
The mammalian transcription factor forkhead box pro-
tein M1 (FOXM1) is an essential effector of G2/M-phase
Fig. 4 FOXM1 is a target of miR-507, and downregulated FOXM1
was analogous to UCA1 depletion and the overexpression of miR-
507. a Predicted binding sites between FOXM1 and miR-507. b The
relative luciferase activities were inhibited in the A375 and SK-MEL-
2 cells transfected with the reporter vector WT FOXM1 30UTR, notwith the reporter vector MT FOXM1 30UTR. c Western blotting
indicated that the FOXM1 protein expression was downregulated in
A375 and SK-MEL-2 cells transfected with si-UCA1, miR-507
mimics and the combination of si-UCA1 and miR-507 mimics,
respectively. d A375 and SK-MEL-2 cells were divided into five
groups including si-NC group, miR-NC group, si-UCA1 group, miR-
507 mimics group and the combination of si-UCA1and miR-507
mimics group. The level of FOXM1 mRNA was examined by qRT-
PCR. e cell proliferation were detected using CCK-8 assay. f transwellassay was performed to investigate changes in cell invasiveness. g the
cell cycle analysis was detected by flow cytometry. *P\ 0.05
Med Oncol (2016) 33:88 Page 7 of 9 88
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transition, mitosis and the DNA damage response [17].
Large quantities of reports have revealed that FOXM1 can
serve as downstream target of miRNA and then participate
in biological functions of the process of cancers. For
example, miR-204 inhibits invasion and epithelial-mes-
enchymal transition by targeting FOXM1 in esophageal
cancer [18]. miR-671-5p inhibits epithelial-to-mesenchy-
mal transition by downregulating FOXM1 expression in
breast cancer [19]. MicroRNA-802 suppresses breast can-
cer proliferation through downregulation of FOXM1 [20].
What’s more, FOXM1 has been verified to be upregulated
in melanoma cells [21] and considered to be a new thera-
peutic target for melanoma [22]. In our experiments, the
level of FOXM1 mRNA was detected to be overexpressed
in melanoma tissues and cells. Bioinformatics analysis and
the dual-luciferase reporter assay were performed to
describe the possibility that FOXM1 would be a target of
miR-507. Next, the data obtained from our studies
demonstrated that FOXM1 can be downregulated by either
miR-507 overexpression or UCA1 depletion, and that
downregulated FOXM1 plays an important role in sup-
pressing cell proliferation, invasion and in inducing cell
cycle arrest in A375 and SK-MEL-2 cell lines.
In conclusion, there exists a UCA1-miR-507-FOXM1
coupling that could inhibit cell proliferation and invasion
and could also induce G0/G1 cell cycle arrest in A375 and
SK-MEL-2 cell lines. A recent study by Sarkar D et al. [23]
has identified lncRNAs, as well as miRNAs, play crucial
roles in epigenetic control with diverse modes action and
functional consequences and the tissue specificities of
miRNAs and lncRNAs make them good candidates for use
as markers for early diagnosis of melanoma. As a result,
our finding might provide some useful evidence about the
lncRNA interaction regulatory network in tumorigenesis of
melanoma, thus it could be argued the UCA1-miR-507-
FOXM1 system may become a new epigenetic therapeutic
target for melanoma treatment.
Acknowledgments The authors are grateful to all staff at the study
center who contributed to this study. This study was supported by a
Grant from the Education Agency of Henan (No. 13A310671).
Compliance with ethical standards
Conflict of interest The authors declare no conflict of interest or
financial disclosures of this study.
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