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Hepatology Research 2015; 45: 128141 doi: 10.1111/hepr.12386

Review Article

miRNA in hepatocellular carcinoma

Asahiro Morishita and Tsutomu Masaki
Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan

Hepatocellular carcinoma (HCC) is the third leading cause of
cancer deaths worldwide. Despite improvements in HCC
therapy, the prognosis for HCC patients remains poor due to a
high incidence of recurrence. An improved understanding of
the pathogenesis of HCC development would facilitate the
development of more effective outcomes for the diagnosis
and treatment of HCC at earlier stages. miRNA are small,
endogenous, non-coding, ssRNA that are 2130 nucleotides
in length and modulate the expression of various target genes
at the post-transcriptional and translational levels. Aberrant
expression of miRNA is common in various human malignan-
cies and modulates cancer-associated genomic regions or
fragile sites. As for the relationship between miRNA and HCC,
several studies have demonstrated that the aberrant expres-
sion of specic miRNA can be detected in HCC cells and
tissues. However, little is known about the mechanisms of
miRNA-related cell proliferation and development. In this
review, we summarize the central and potential roles of
miRNA in the pathogenesis of HCC and elucidate new possi-
bilities that may be useful as diagnostic and prognostic
markers, as well as novel therapeutic targets in HCC.
Key words: diagnostic and prognostic markers,
hepatocellular carcinoma, miRNA, therapeutic target

INTRODUCTION miRNA can promote the targeting and modulation of

more than 200 mRNA.6,7 In humans, a total of 2000

M IRNA ARE SMALL, interfering, non-coding RNA

that are 2130 nucleotides in length, and it has
been predicted that there are approximately 1000 of
miRNA have been discovered.8
Although their importance is recognized in regulating
protein-coding gene expression, the precise functions of
these sequences in the human genome.1 Each miRNA
miRNA remain elusive. It is now apparent that miRNA
negatively regulates its target genes by binding to mul-
play an important role in human carcinogenesis.6,912
tiple mRNA. Binding between miRNA and mRNA trig-
In addition, the expression of miRNA is generally
gers the RNA-mediated RNAi pathway, in which the
downregulated in tumor tissues compared with normal
mRNA transcripts are cleaved by an miRNA-associated
tissues, indicating that a subset of miRNA act as tumor
RNA-induced silencing complex (miRISC).2 In most
suppressors. Therefore, the discovery of miRNA has
animals, single-stranded miRNA act by binding to
expanded our knowledge of post-transcriptional gene
imperfectly complementary sites within the 3-
regulation during cancer development. Interestingly,
untranslated regions of their target mRNA, inhibiting
more than half of all genes that encode miRNA are
translation or initiating degradation via the miRISC.3
located at fragile sites or in cancer-associated regions of
Recruitment of the miRISC can modulate the expression
the genome,13 suggesting that miRNA may serve as diag-
of targeted protein-coding genes.4,5 Surprisingly, each
nostic markers or therapeutic targets. The first report of
altered miRNA expression in cancer involved a frequent
chromosomal deletion and two miRNA, miRNA-15
Correspondence: Profesor Tsutomu Masaki, Department of (miR-15) and miRNA-16 (miR-16), thought to target
Gastroenterology and Neurology, Kagawa University School of
Medicine, 1750-1 Ikenobe, Miki-cho, Kida-gun, Kagawa 761-0793,
B-cell lymphoma 2 (BCL-2), which is the anti-apoptotic
Japan. Email: asahiro@med.kagawa-u.ac.jp factor in chronic lymphocytic leukemia.14 Recent reports
Received 27 June 2014; revision 27 June 2014; accepted 1 July 2014. have shown that miRNA are associated with the

128 2014 The Authors.

Hepatology Research published by Wiley Publishing Asia Pty Ltd on behalf of The Japan Society of Hepatology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs
License, which permits use and distribution in any medium, provided the original work is properly cited, the use is
non-commercial and no modifications or adaptations are made.
Hepatology Research 2015; 45: 128141 A. Morishita and T. Masaki 129

pathogenesis of various types of cancers,912 and these
findings have increased our understanding of epigenetic
modification during oncogenesis.2
Several studies have recently reported a relation-
ship between miRNA and hepatocellular carcinoma
(HCC).12,1518 Among several miRNA implicated in HCC,
including miR-21, miR-221 and miR-222, the aberrant
levels of miRNA expressions were upregulated.12,16,17
However, other miRNA, including miR-122a, miR-145,
miR-199a and miR-223, were decreased in HCC com-
pared to normal tissues.15,19 Surprisingly, Huang et al.
have shown that, among aberrant miRNA in HCC, miR-
338 affects several clinical features, such as tumor size,
tumornodemetastasis classification, vascular invasion
and intrahepatic metastasis.18 These studies suggest that
the modulation of miRNA may play an important role in
the progression of HCC.
BIOGENESIS AND REGULATION OF miRNA
S EVERAL STEPS ARE involved in the biogenesis
of miRNA: transcription, cleavage, export, further
cleavage, strand selection and interaction with mRNA
(Fig. 1).20 The genes encoding miRNA are primarily tran-
scribed by RNA polymerase II into initial transcripts that
are then processed through the canonical pathway
or the mirtron pathway to form primary miRNA
transcripts (pri-miRNA) that include one or more
hairpin structures.21 These pri-miRNA are capped at the
5-end and polyadenylated at the 3-end22 and then

Nucleus Cytoplasm

Genome DNA Translational repression mRNA degradation

Pol II
RISC

AGO RISC formation

Transcription

AGO Mature miRNA

Pri-miRNA
Unwinding Degradation
m7G AAAAA

miRNA duplex
Clevage
Clevage

Pre-miRNA
Exportin 5 Export
Drosha DGCR8 TRBP Dicer

Figure 1 Steps in biogenesis of miRNA. The primary miRNA (pri-miRNA) is transcribed from genome DNA mainly by RNA
polymerase II (Pol II). The DroshaDGCR8 complex cleaves and splices pri-miRNA into hairpin-like miRNA precursors called
pre-miRNA. These pre-miRNA are exported from the nucleus to the cytoplasm in an Exportin-5-Ran-guanosine-5-triphosphate
(GTP)-dependent manner. In the cytoplasm, Dicer and TRBP cleaves hairpin structure of pre-miRNA into mature miRNA. The
processed miRNA are then loaded onto the RNA-induced silencing complex (RISC) with Argonaute (Ago2) and are guided to their
mRNA targets for translational repression or mRNA degradation.

2014 The Authors.

Hepatology Research published by Wiley Publishing Asia Pty Ltd on behalf of The Japan Society of Hepatology
130 A. Morishita and T. Masaki
cleaved into approximately 70-nucleotide (nt) hairpin-
structured precursors (pre-miRNA) with a 5-phosphate
and a 3-2-nt overhang by a multiprotein complex
that includes an RNase III enzyme named Drosha
and a dsRNA-binding domain protein (dsRBD) named
DGCR8/Pasha.23 Subsequently, exportin-5 trans-
locates pre-miRNA from the nucleus to the cytoplasm
through a Ran-guanine-triphosphate (GTP)-dependent
mechanism.24 These translocated pre-miRNA are cleaved
by a second RNase III endonuclease named Dicer and
the dsRBD proteins TRBP/PACT.25 Finally, one strand of
the pre-miRNA interacts with the Argonaute (AGO)
protein and is degraded in the RNA-induced silencing
complex that modulates mRNA degradation and trans-
lational repression.26
In addition to the canonical miRNA pathway, some
miRNA are processed into miRNA-like molecules
in a Microprocessor-independent manner, including
certain snoRNA,27 tRNA28 and endogenous shRNA.29
Furthermore, more than 1 million Drosophila small-
RNA sequences were recently generated using 454
pyrosequencing, and these sequences identified 14 short
introns with predicted hairpin structures.30 These short
introns were named mirtrons after analyzing their
characteristics. Primary mirtron precursors include
mirtronic introns and flanking exonic sequences that
typically lack the lower stem (11 bp) that is found in
miRNA, which mediates their recognition and cleavage
via the Pasha (DGCR8)/Drosha complex.31 The AG
splice acceptor of a typical mirtron adopts a 2-nt
3-overhang for these hairpins, allowing mirtronsto
enter the miRNA-processing pathway without Drosha-
mediated cleavage.32
miRNA regulate various biological processes by
modulating specific mRNA, and their expression is
tightly regulated in normal cells.29,33 Each miRNA can
potentially be controlled independently at the transcrip-
tional level by various regulators or at the epigenetic
level via DNA methylation.3335 Interestingly, the regula-
tory elements that control protein-coding genes, such as
CpG islands, TATA boxes, transcription factor II B rec-
ognition sites, initiator elements and histone modifica-
tions, are also found in the promoters of miRNA
genes,36 indicating that the transcription factors are
similar between protein-coding genes and miRNA.
Therefore, the expression of various processing compo-
nents is simultaneously regulated to modulate the activ-
ity of mature miRNA.
In addition, miRNA can also autoregulate their own
transcription by controlling various transcription factors
in positive or negative feedback loops. The miR-200
Hepatology Research published by Wiley Publishing Asia Pty Ltd on behalf of The Japan Society of Hepatology
Hepatology Research 2015; 45: 128141
family of miRNA plays an important role by inhibiting
the expression of zinc finger E-box-binding homeobox
1 (ZEB1) and survival of motor neuron protein-
interacting protein 1 (SIP1), which act as transcriptional
repressors in epithelial cells, to regulate the epithelial to
mesenchymal transition; however, ZEB1 and SIP1 also
suppress the miR-200 family, including miR-200a and
miR-200b, by binding their promoter regions.37 This
result indicates that miRNA and their target molecules
are tightly regulated by each other at the transcription
level.
Moreover, miRNA are also regulated by epigenetic
processes, such as DNA methylation and specific
histone deacetylation. Seventeen of the 313 human
miRNA were upregulated more than threefold after
treatment with the chromatin-modifying drugs 5-aza-
2-deoxycytidine and 4-phenylbutyric acid. Among
these miRNA, miR-127 was highly upregulated after
treatment.38 In addition, inhibiting histone deacetylases
rapidly downregulated 22 miRNA and upregulated five
miRNA.39
Furthermore, miRNA expression is also controlled
at the post-transcriptional level. A large fraction of
miRNA genes are post-transcriptionally regulated,
including those of the Let-7 family.40 Individual miRNA
expression processed from the same pri-miRNA is occa-
sionally different at the mature miRNA level.41 Initially
during post-transcriptional regulation, miRNA are pro-
cessed by Microprocessor, which consists of Drosha
and the dsRNA-binding protein DGCR8 in the
nucleus.23 A loss of Drosha or DGCR8 function leads to
a decrease in pre-miRNA and mature miRNA.23 In the
cytoplasm, pre-miRNA that are exported from the
nucleus in a Ran/GTP/Exportin-5-mediated event are
further regulated by the RNase III enzyme Dicer to
become mature RNA.40
MIRNA EXPRESSION AND
HCC DEVELOPMENT
M IRNA HAVE BEEN reported to influence the criti-
cal functions of cellular differentiation, prolifera-
tion, apoptosis, invasion and metastasis.42 The miRNA
expression profiles in tumors are different from those in
normal tissues and also vary according to the type of
tumor. Interestingly, the direct targets of miRNA are also
protein-coding genes of the cell cycle, apoptosis and
metastasis in HCC.43 Recently, microarray analysis has
revealed that a subset of miRNA are up- and
downregulated during the development of HCC.44
Reductions in the expression of miRNA are frequently
2014 The Authors.
Hepatology Research 2015; 45: 128141
observed in HCC, and the targets of these down-
regulated miRNA may be putative oncogenes. Con-
versely, some of the upregulated miRNA act as
oncogenic miRNA in HCC and may be targets of tumor
suppressor genes.
miRNA are associated with various chronic liver dis-
eases, such as alcoholic liver disease,45 non-alcoholic
steatohepatitis (NASH)4648 and viral hepatitis.4951 In
addition to these chronic diseases, miRNA are also
involved in the development of HCC. In alcoholic liver
disease, miR-217 induces ethanol-induced fat accumu-
lation in hepatocytes by inhibiting the expression
of SIRT1.45 The miRNA miR-126, miR-27b, miR-182,
miR-183, miR-199, miR-200a, miR-214 and miR-322
were downregulated in alcohol-related HCC.51,52 The
observed reduction in miR-27 in alcoholic steato-
hepatitis was the result of epigenetic events that
occurred in response to alcohol.53
The development and exacerbation of NASH, both
of which are also associated with miRNA, increase
the risk of HCC. A recent study indicated that miRNA
play a critical role in activating hepatic stellate cells
(HSC) during the development of NASH.54 Free
cholesterol was observed to accumulate due to an
enhancement of both sterol regulatory element-
binding protein-2 (SREBP2) and miR-33a signaling via
the inhibition of peroxisome proliferator-activated
receptor- signaling together with HSC activation
and disruption of the SREBP2-mediated cholesterol-
feedback system in HSC.54 The upregulation of miR-21,
which downregulates the expression of tumor sup-
pressor phosphatase and tensin homolog (PTEN), is
induced by unsaturated fatty acids in hepatocytes.46 In
addition, miR-155 suppresses another tumor suppres-
sor gene, CCAAT-enhancer-binding protein-, and has
been also shown to be upregulated in mice fed a
choline-deficient amino acid-defined diet.47,48
Viral hepatitis, such as that caused by the hepatitis B
virus (HBV) and hepatitis C virus (HCV), is the most
frequent cause of HCC and cirrhosis.55 The 5-year
cumulative risk of hepatocarcinogenesis with liver cir-
rhosis ranges 530%.55 Among HBV cases, only two
miRNA, miR-210 and miR-199-3p, were observed to
affect HBV gene expression and replication in an
experimental model. In contrast, many cellular miRNA
indirectly regulate the HBV life cycle by affecting virus-
relevant cellular proteins.56 Ura et al. examined the
expression of 188 miRNA in HCC and adjacent normal
tissues obtained from 12 HBV positive and 14 HCV
positive patients. In these groups, the expression of six
miRNA was decreased in HBV patients, and that of 13
Hepatology Research published by Wiley Publishing Asia Pty Ltd on behalf of The Japan Society of Hepatology
A. Morishita and T. Masaki 131
miRNA was reduced in HCV patients.57 These data
suggest that there are distinct patterns in the miRNA
profiles between HBV and HCV infection. Several
reports demonstrated that miR-96 or miR-26 were sig-
nificantly upregulated in HBV-related HCC tissues.52,58
Takazawa et al. reported comprehensive miRNA pro-
files using sequencing methods that provided more
than 314 000 reliable reads from HCC tissue and more
than 268 000 reliable reads from adjacent normal liver.
Bioinformatic-based analysis revealed several miRNA
altered in HCC, including miR-122, miR-21 and miR-
34a.59 Therefore, further studies that characterize the
miRNA associated with HBV-related HCC may yield a
novel therapeutic tool for HCC patients with HBV
infection.
In addition, miR-196 plays an important role through
the inhibition of Bach1 (a basic leucine zipper mamma-
lian transcriptional repressor) and upregulation of
hemeoxygenase 1 in HCV-related HCC.60 Diaz et al. also
demonstrated 18 miRNA among 2226 human miRNA
that were exclusively expressed in HCV-related HCC.61
One of these 18 miRNA has been associated with net-
works that include p53, PTEN and retinoic acid and is
involved in the pathogenesis of HCC.62,63 These data
suggest that miRNA pathways are essential to the devel-
opment of HCC during HCV infection.
CLINICAL SIGNIFICANCE OF MIRNA IN HCC
Single nucleotide polymorphisms of miRNA
and the risk of HCC
S INGLE NUCLEOTIDE POLYMORPHISMS in
miRNA and their targets have been associated with
an increased risk of HCC. Because miRNA must closely
recognize binding sites in their target genes, a variation
in even 1 nt may produce dramatic changes in the
post-transcriptional regulation of target genes. Poly-
morphisms in miR-101-1/rs7536540,64 miR-101-2/
rs12375841,64 miR-34b/c/rs493872365 and miR-106b-
25-cluster/rs99988566 are positively associated with an
increased risk of HCC. In contrast, miR-371373/
rs385950167 and miR-149c/rs229283268 are negatively
involved in HCC risk. However, conflicting results were
obtained from several studies, such as with miR-499a/
rs37464446870 and miR-196a-2/rs11614913.68,7173
miRNA as biomarkers for HCC
miRNA can be characterized as prognostic or diagnostic
markers. Downregulation of the miRNA miR-let-7g,74
miR-22,75 miR-26,58 miR-29,76 miR-99a,77 miR-122,78
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132 A. Morishita and T. Masaki Hepatology Research 2015; 45: 128141

Table 1 Downregulated miRNA in hepatocellular carcinoma

miRNA Targets Mechanisms References
50,83,84
let-7a Caspase-3, STAT3 Apoptosis, proliferation
85
let-7b HMGA2 Apoptosis, proliferation
51,86,87
let-7c Bcl-xL, c-Myc Apoptosis, proliferation, cell growth
50
let-7d Apoptosis, proliferation
50
let-7f-1 Apoptosis, proliferation
74,88,89
let-7g Bcl-xL, c-Myc, COLIA2, p16 Apoptosis, metastasis
90
miR-1 ET-1 Proliferation
91
miR-7 PIK3CD
92
miR-10a EphA4
93
miR-10b
94
miR-15a/16
52
miR-21
9597
miR-26a CDK6, IL-6, cyclin D2, E1, E2 Cell cycle
98
miR-29a SPARC Proliferation
99
miR-29b MMP-2 Invasion
100
miR-29c SIRT1
101,102
miR-34a c-Met, CCL22 Metastasis
77,103
miR-99a PLK1, IGF-1R
103
miR-100 PLK1 Carcinogenesis
104106
miR-101 EZH2, EED, Mcl-1, Fos, Apoptosis, DNA methylation
miR-122 Bcl-w, ADAM17, Wnt1 Apoptosis, proliferation, angiogenesis 107110

111
miR-124 PIK3CA Proliferation
112,113
miR-125a MMP11, VEGF-A,SIRT7 Proliferation, metastasis, metabolism
51,113117
miR-125b Mcl-1, Bcl-w, SUV39H1, SIRT7 Proliferation, metastasis, angiogenesis, apoptosis,
histone modification
51,118,119
miR-139 ROCK2, c-Fos Metastasis
51
miR-139-5p
120,121
miR-140-5p TGFR1, FIF9, DMMT1
122
miR-141 DLC-1
miR-145 IRS1/2, IGF-1R, -catenin 81,123

124127
miR-148a c-Met, HRIP, E-cadherin, c-Myc
128
miR-152 DNMT1, GSTP1, CDH1
129,130
miR-195 cyclin D1, CDK6, E2F3, LATS2 Cell cycle, tumorigenesis, apoptosis
17
miR-198
131133
miR-199a-3p mTOR, PAK4, caveolin-2 Drug resistance, cell growth
134,135
miR-199a-5p DDR1, ATG7 Invasion, autophagy
136
miR-199b Proliferation, invasion, apoptosis
137
miR-200a HDAC4 Proliferation, metastasis
51
miR-200b
52
miR-200c
138
miR-203 Surviving Proliferation
miR-214 HDGF, -catenin Cell growth, angiogenesis, metastasis 139141

142
miR-219-5p GPC3 Proliferation
52
miR-222
16
miR-223 STMN1 Proliferation
143
miR-224
127
miR-363-3p c-Myc
144,145
miR-375 ATG7, AEG-1 Autophagy
146
miR-376a PIK3R1 Apoptosis, proliferation
147
miR-429 Rab18
148
miR-449 c-Met Proliferation, apoptosis
149
miR-450a DNMT3a Proliferation
150,151
miR-520b/e NIK, MEKK2, cyclin D1 Cell growth, proliferation
152
miR-612 AKT2
153
miR-637 STAT activation
93
miR-1271 GLP3

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Hepatology Research 2015; 45: 128141 A. Morishita and T. Masaki 133

miR-124,79 miR-139,80 miR-14581 and miR-199b82
has been implicated in cell proliferation, apoptosis,
angiogenesis, recurrence, shorter disease-free survival
and poor prognosis (Table 1). In contrast, upregulation
of miR-10b,154 miR-17-5p,155 miR-21,156 miR-135a,157
miR-155,158 miR-182,159 miR-221156 and miR-222118,156
has been associated with metastasis, angiogenesis and
poor prognosis (Table 2). In addition, miRNA profiling
classified HCC into three main clusters.189 These results
indicate the potential value of miRNA detection for the
prediction of survival in HCC. Furthermore, Yamamoto
et al. reported that miR-500 was increased in the sera of
HCC patients and decreased after surgical treatment.196
In addition, other miRNA, such as miR-25, miR-375 and
let-7f, can be used to distinguish HCC from normal
control tissue.197 Interestingly, extracellular miRNA are

Table 2 Upregulated miRNA in hepatocellular carcinoma

miRNA Targets Mechanisms References
92,154
miR-10a EphA4; CADM1 EMT, metastasis
160
miR-17-5p p38 pathway Migration
49
miR-18a ER1a Proliferation
12,48
miR-21 PTEN; RHOB; PDCD4 Metastasis, drug resistance
161
miR-22 Era, IL-1a Carcinogenesis
162
miR-23a PGC-1a, G6PC Gluconeogenesis
96,97
miR-26a IL-6, CyclinD2, E2 Tumor growth, metastasis
163
miR-30d GNAI2 Invasion, metastasis
17
miR-100 PLK1 Carcinogenesis
164
miR-106b APC Proliferation
165
miR-130b TP53INP1 Cell growth, self-renewal
157
miR-135a FOXM1, MTSS1 Metastasis
166
miR-143 FNDC3B Metastasis
167,168
miR-151 FAK, RhoGDIA Migration
48,169,170
miR-155 SOCS1, DKK1, APC, PTEN Proliferation; tumorigenesis
171
miR-181b TIMP3 Tumorigenesis, metastasis
159
miR-182 MTSS1 Metastasis
172
miR-183 AKAP12 Carcinogenesis
172
miR-186 AKAP12 Carcinogenesis
173
miR-200 NRF2 pathway Carcinogenesis
174
miR-210 VMP1 Metastasis
175
miR-216a TSLC1 Carcinogenesis
176
miR-216a/217 PTEN, SMAD7 EMT, drug resistance
177179
miR-221 p27, p57, Arnt, CDK inhibitors Apoptosis, proliferation, angiogenesis
180
miR-221/222 p27, DDIT4 Tumorigenesis
181,182
miR-224 Atg5, Smad4, autophagy, API-5 Tumorigenesis, autophagy
183
miR-301a Gax Metastasis
184
miR-373 PPP6C Cell cycle
185
miR-423 p21/waf1 Cell growth
186
miR-485-3p MAT1, LIN28B Cell growth, EMT
187
miR-490-3p ERCIC3 EMT
188
miR-494 MCC Tumorigenesis
186
miR-495 MAT1, LIN28B Tumorigenesis, metastasis
189
miR-517a Tumorigenesis, metastasis
190
miR-519d p21, PTEN, AKT3, TIMP2 Proliferation, invasion, apoptosis
191
miR-550a CPEB4 Proliferation, invasion, metastasis
192
miR-590-5p TGF- RII Metastasis, proliferation
193
miR-615-5p IGF-II Proliferation, migration
194
miR-657 TLE1, NF-B Proliferation
186
miR-664 MAT1, LIN28B Tumorigenesis, metastasis
195
miR-1323 Proliferation

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Hepatology Research published by Wiley Publishing Asia Pty Ltd on behalf of The Japan Society of Hepatology
130 A. Morishita and T. Masaki
stable in circulation, indicating that miRNA may serve as
useful diagnostic markers for HCC.
miRNA as targets for HCC treatment
Because miRNA function as oncogenes or tumor sup-
pressors, alterations in these miRNA influence the
malignant phenotypes of HCC cells. In tumor tissues,
miRNA associated with tumor suppressors are down-
regulated during tumorigenesis, tumor development
and metastasis. These miRNA may be potential thera-
peutic targets, and strategies for miRNA replacement
therapies have been developed using miR-26a,95 miR-
122198 and miR-124111 in a HCC mouse model. In
contrast, inhibition of miR-221 lengthened survival,
reduced the nodule number and retarded tumor devel-
opment.177,199 Furthermore, no toxicity was observed
when miRNA-targeted therapy was used to treat HCC in
a mice model. miRNA have been also shown to affect
the sensitivity of tumors to anticancer drugs. Several
reports have indicated that miRNA profiles are
dramatically altered following metformin treatment for
various cancers: gastric cancer,200 esophageal cancer201
and HCC.202 Interestingly, overexpression of miR-21203
and miR-181b171 induced resistance to interferon5-
fluorouracil combination therapy and doxorubicin
treatment in HCC. In contrast, Bai et al. demonstrated
that restoring expression of the tumor suppressive miR-
122 makes HCC cells more sensitive to sorafenib via the
downregulation of multidrug resistance genes.
CONCLUSION
M IRNA ARE BEING considered as new biomarkers
and potential therapeutic targets for HCC. To date,
many miRNA have been identified as regulators of
various target genes during HCC development. In addi-
tion, although miRNA-based therapy is not currently
used in the clinic, its innovative applications are growing
in various fields. However, the details regarding
targetable miRNA and the mechanisms of miRNA-
induced anticancer effects remain unclear. Further analy-
ses and new technology for miRNA research will
elucidate novel concepts in the pathogenesis of HCC.
Consequently, analyzing miRNA profiles and their sig-
naling pathways offers deeper insights into the treatment
options for HCC.
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