ONCOLOGY REPORTS 27: 1759-1764, 2012
Abstract. microRNAs (miRNAs) are small non-coding
RNAs that regulate target gene expression. It is known that
miRNA-107 (miR-107) promotes cancer invasion and metas-
tasis. However, the relationship between clinicopathological
factors and the prognostic significance of miR-107 for gastric
cancer patients remains elusive. In this study, we evaluated the
prognostic value of miR-107 using tissue samples from gastric
cancer patients. Furthermore, the relationship between miR-107
and the mRNA levels of its target gene DICER1 was exam-
ined. The expression levels of miR-107 and DICER1 mRNA in
tumor tissues and adjacent normal tissues of 161 gastric cancer
patients were examined (TNM stage I, 29 patients; stage II,
31 patients; stage III, 51 patients and stage IV, 50 patients).
miR-107 levels were measured by TaqMan microRNA assays,
and DICER1 mRNA levels were measured by the TaqMan
real-time RT-PCR method. In the analysis by real-time
PCR-based miRNA arrays using pooled RNA samples from
five gastric cancer patients, expression of miR-107, miR-21,
miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150,
miR-191 and miR-17 was found to be upregulation. The
mean expression level of miR-107 was significantly higher in
the tumor tissues compared to that of normal tissues. In the
comparison of clinicopathological factors, miR-107 expression
showed significant association with depth of tumor invasion,
lymph node metastasis and stage. In Kaplan-Meier survival
curve analysis, overall survival rates (OS) and disease-free
survival rates (DFS) of patients with high miR-107 expres-
sion were significantly worse than those of patients with low
miR-107 expression. In the Cox multivariate analysis, it was
shown that miR-107 expression in gastric cancer tissues was
an independent prognostic factor for OS and DFS. Significant
inverse correlations were demonstrated between miR-107
and DICER1 mRNA. Our results indicate that miR-107 may
be useful as an effective biomarker for prediction of a poor
prognosis in gastric cancer patients.
Gastric cancer is one of the most common cancers in Japan
and other East Asian countries (1). Despite significant invest-
ment and advances in the management of gastric cancer, the
survival rates for patients with advanced stages of the disease
have changed little over the past 10 years (2). As such, a
biomarker for selection of high-risk patients with poor prog-
nosis is highly desirable.
microRNAs (miRNAs) are small 21-25 nucleotides of
RNA that participate in the regulation of cell differentiation,
cell cycle progression, apoptosis and tumorigenesis (3-8).
The study of microRNA has been extended to many types
of cancer. miRNAs target protein-coding mRNAs at the
post-transcriptional level by direct cleavage of the mRNA
or by inhibition of protein synthesis (9,10). Recent evidence
indicates that various miRNAs can function as oncogenes
or tumor-suppressor genes and play a central role in carci-
nogenesis (5). Accumulating evidence shows that miR-107
is one of the oncogenic RNAs, and overexpression of these
RNAs has been reported in several types of human malignant
solid tumors, including gastric, esophageal, pancreatic and
colorectal cancer (10-16). Moreover, miR-107 may contribute
to the regulation of the cell cycle in non-small cell lung cancer
cell lines (17). It was reported that miR-107 can mediate p53
regulation of hypoxic signaling and tumor angiogenesis (18).
Additionally, miRNAs may be useful tools for characterizing
specific cancers and for determining patient prognosis and
response to therapy (3-8). In gastric cancer, it has been shown
that overexpression of miR-107 is associated with metastasis
(13). However, the association between the miR-107 expres-
sion, clinicopathological characteristics and the prognostic
value of miR-107 in gastric cancer has not yet been reported.
miRNAs exert their biological effects by targeting specific
mRNAs. DICER1 is known as one of the target genes of
miR-107 (13). Dicer is the enzyme responsible for the cleavage
of miRNA precursors. Growing evidence suggests that
DICER1 expression levels are associated with worse clinical
outcomes in various cancer types (19-22). However, there
are few studies concerning the correlation between DICER1
Clinicopathological and prognostic significance of microRNA-107
and its relationship to DICER1 mRNA expression in gastric cancer
TAISUKE INOUE, HISAE IINUMA, ETSUSHI OGAWA, TSUYOSHI INABA and RYOJI FUKUSHIMA
Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan
Received September 5, 2011; Accepted November 4, 2011
Correspondence to: Dr Hisae Iinuma, Department of Surgery,
Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku,
Tokyo 173-0003, Japan
Abbreviations: RT-PCR, reverse transcription-polymerase chain
reaction; miRNA, microRNA
Key words: gastric cancer, microRNA-107, DICER1, recurrence,
INOUE et al: PROGNOSTIC VALUE OF microRNA-107 IN GASTRIC CANCER
multivariate analysis of miR-107. In contrast, in our present
study of 161 gastric cancer patients, we analyzed not only the
Kaplan-Meier survival curve but also applied Cox multivariate
analysis to clarify the prognostic value of miR-107. Notably,
we found that higher expression levels of miR-107 in gastric
cancer tissues significantly correlated with poorer OS and DFS.
Furthermore, in Cox multivariate analysis, miR-107 expression
in gastric cancer tissues showed a significant association with
OS and DFS. Although, our results are different from those
of Li et al, our results support the hypothesis that miR-107
promotes gastric cancer metastasis by downregulation of
DICER1 (13). However, an explanation for the discrepancy in
the survival results between ours and other studies must await
further research. To the best of our knowledge, our study is the
first to show the independent prognostic value of miR-107 in
gastric cancer patients.
miRNAs exert their biological effects by targeting protein-
coding-specific mRNAs in two different ways: one by direct
cleavage of the target mRNAs and the other by inhibition
of protein synthesis (8). Recently, Li et al demonstrated that
miR-107 regulates tumor invasion and metastasis by targeting
DICER1 in gastric cancer (13). Dicer is the enzyme respon-
sible for the cleavage of miRNA precursors and it is necessary
for the production of mature miRNAs (25). DICER1 is capable
of splicing the hairpin-like structure RNA and double-strand
RNA into mature 21-nt miRNA or siRNA. Although research
on the association of DICER1 with disease is limited, DICER1
appears to play an important role in the development of cancer
(18-21). A different transcription initiation site and splicing of
the DICER1 gene which may result in poor protein transla-
tion and stability of mRNA and subsequent lower expression
of DICER1 in cancer cells was suggested (26). Furthermore,
DICER1 expression was found to be decreased during the
progression of gastric cancer (27). However, little is known
concerning the relationship between miR-107 and DICER1
mRNA expression in clinical samples of gastric cancer
patients. In the present study, we examined the relationship
between miR-107 and DICER1 mRNA levels, and demon-
strated a significant inverse correlation.
In conclusion, our data indicate that overexpression of
miR-107 in gastric cancer tissues has prognostic value and
that these molecules may have useful therapeutic applications
in the future.
We thank J. Tamura for her excellent technical assistance, and
all members of the gastrointestinal group for sampling and
clinical suggestions. This study was supported by a Grant-
in-Aid for Scientific Research (C) (21591734).
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