MicroRNAs in normal and cancer cells: a new class of gene expression regulators
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. This review describes miRNA biogenesis, their functions i...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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irk-123456789-1375822018-06-18T03:03:52Z MicroRNAs in normal and cancer cells: a new class of gene expression regulators Bagnyukova, T.V. Pogribny, I.P. Chekhun, V.F. Reviews MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. This review describes miRNA biogenesis, their functions in normal cells, and alterations of miRNA sets in cancer and roles of antitumorigenic and oncogenic miRNAs in cancer development. Микро PHK(miRNAs) — это малое не кодирующие РНК, негативно регулирующие экспрессию генов на посттранскринц ионном уровне и принимаюшие участие в развитии, лифферешшровке. пролиферации и апоптозе клеток, а также выполняющие важную роль в опухолевом процессе. В обзоре обсужден биогенез miRNA, функции этих молекул в нормальных клетках, изменения набора miRNA в опухолевых клетках и роль противоопухолевых и онкогенных nnRNAs в опухолевой прогрессии. Ключевые сюва: микроРНК, рак. онкоген, опухолевый супрессор. 2006 Article MicroRNAs in normal and cancer cells: a new class of gene expression regulators / T.V. Bagnyukova, I.P. Pogribny, V.F. Chekhun // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 263-269. — Бібліогр.: 101 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137582 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Reviews Reviews Bagnyukova, T.V. Pogribny, I.P. Chekhun, V.F. MicroRNAs in normal and cancer cells: a new class of gene expression regulators Experimental Oncology |
| description |
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. This review describes miRNA biogenesis, their functions in normal cells, and alterations of miRNA sets in cancer and roles of antitumorigenic and oncogenic miRNAs in cancer development. |
| format |
Article |
| author |
Bagnyukova, T.V. Pogribny, I.P. Chekhun, V.F. |
| author_facet |
Bagnyukova, T.V. Pogribny, I.P. Chekhun, V.F. |
| author_sort |
Bagnyukova, T.V. |
| title |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators |
| title_short |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators |
| title_full |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators |
| title_fullStr |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators |
| title_full_unstemmed |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators |
| title_sort |
micrornas in normal and cancer cells: a new class of gene expression regulators |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2006 |
| topic_facet |
Reviews |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137582 |
| citation_txt |
MicroRNAs in normal and cancer cells: a new class of gene expression regulators / T.V. Bagnyukova, I.P. Pogribny, V.F. Chekhun // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 263-269. — Бібліогр.: 101 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT bagnyukovatv micrornasinnormalandcancercellsanewclassofgeneexpressionregulators AT pogribnyip micrornasinnormalandcancercellsanewclassofgeneexpressionregulators AT chekhunvf micrornasinnormalandcancercellsanewclassofgeneexpressionregulators |
| first_indexed |
2025-07-10T02:37:38Z |
| last_indexed |
2025-07-10T02:37:38Z |
| _version_ |
1837225800380710912 |
| fulltext |
Experimental Oncology ���� ��������� ���� ��ecem�er�� ������� ��������� ���� ��ecem�er�� ����ecem�er�� ����� ��� ���
MicroRNAs are a novel class of small�� ~ 1���5 nu-
cleotides long�� non-coding RNAs that post-trans-
criptionally negatively regulate gene expression. The
first miRNA�� lin-4�� was discovered in 1��� in Cae-
norhabditis elegans [���� �5]. The lin-4 miRNA gene
encodes a ��-nucleotide non-coding RNA that nega-
tively regulates the translation of another gene�� lin-14��
�y �ase-pairing to complementary sites within its
�´-untranslated region ��´-UTR�� affecting the develop-
ment timing. This type of regulation is an exception
from the accepted concept of gene expression regula-
tion. However�� a significant num�er of recent studies
have demonstrated that miRNA-mediated regulation
of gene expression is a wide-spread phenomena in
eukaryotic organisms that control the fundamental
cellular processes such as development�� proliferation��
and apoptosis [�]. Moreover�� altered miRNA profiles
have �een found in a variety of cancers indicating
their significant role in cancer development [���� �5].
Hundreds of miRNAs have �een identified in animals��
plants and viruses�� among them > ��� miRNA genes in
the human genome [7]. Many miRNAs are highly con-
served �etween variety of evolutionary distinguished
species [�] supporting the hypothesis a�out important
functions of these small molecules in organisms. In this
review�� we descri�e miRNA �iogenesis�� their functions
in the cell�� paying special attention to tumor cells.
miRNA biogeNesis ANd modes
of ActioN
miRNA genes are located mainly within introns of
protein-coding and non-coding sequences�� as well
as in intergenic regions [�1�� 1��]. In the first case��
expression of corresponding miRNAs may �e linked
with transcriptional regulation of their host genes and��
hence�� reveals tissue specificity due to expression of
different sets of genes [��� ���� �7]. In the second case��
expression of miRNAs is regulated independently
via their own regulatory elements [1��]. In addition��
a recent study has shown that a num�er of mammalian
miRNAs are derived from �NA repetitive sequences��
including LINE-� transposa�le elements [��]. miRNAs
are transcri�ed �y RNA polymerase II producing long
primary-miRNAs �pri-miRNAs�� [5�]. Within a pri-miRNA��
the miRNA itself forms a stem-loop hairpin structure
�Figure���� which is excised in the nucleus �y the RNase III
endonuclease �rosha associated with dou�le-stranded
RNA-�inding domain-containing protein �GCR� �in
mammals�� or Pasha �in Drosophila and C. elegans��
[���� ��]. �rosha asymmetrically cleaves �oth strands
of the hairpin stem-loop at sites near the �ase of the
primary stem-loop resulting in release ���7�-nucleo-
tide pre-miRNA [�1]. Pre-miRNA is exported to the
cytoplasm �y Ran-GTP-dependent Exportin-5 complex
[��]. The cytoplasmic RNase III endonuclease �icer1
with associated proteins TRBP and PACT in mammals
excises a RNA-hairpin duplex from pre-miRNA. The
fully mature miRNA incorporates in a single-stranded
form into ri�onucleoprotein complex termed as the
RNA-induced silencing complex �RISC��. In mammals��
miRNAs negatively regulate their targets �y either
�inding to imperfect complementary sites within the
�´-untranslated regions of their mRNA-targets [17]�� or
�y targeting specific cleavage of homologous mRNAs
[��]. In the first case�� miRNAs reduce protein levels of
target genes �y post-transcriptionally repressing target-
gene expression without affecting mRNA levels of these
genes�� whereas in the second case�� miRNAs induce the
degradation of target mRNAs �y the RISC. Interestingly��
that miR-1�� positively affects the replication of hepa-
titis C virus �y �inding to its 5´-noncoding region [4�].
It is unclear whether this effect is unique or represents
an unknown yet mechanism of miRNA action.
To date�� many details of miRNA-mediated gene
expression regulation have �een clarified. In contrast��
regulation of miRNA expression is not fully understood.
Epigenetic alterations play an important role in general
regulation of gene expression [4�]�� �ut little attention
has �een paid to miRNA genes. A recent study con-
microRNAs iN NoRmAl ANd cANceR cells: A New clAss
of geNe expRessioN RegulAtoRs
T.V. Bagnyukova1, 2, I.P. Pogribny2, V.F. Chekhun3, *
1Department of Biochemistry, Precarpathian National University, Ivano-Frankivsk 76025, Ukraine
2Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
3Department of Mechanisms of Anticancer Therapy, R.E. Kavetsky Institute of Experimental Pathology,
Oncology and Radiobiology, Kyiv 03022, Ukraine
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. They
are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. This review
describes miRNA biogenesis, their functions in normal cells, and alterations of miRNA sets in cancer and roles of antitumorigenic
and oncogenic miRNAs in cancer development.
Key Words: microRNA, cancer, oncogene, tumor suppressor.
Received: November 1, 2006.
*Correspondence: Fax: +380 44 2581656
E-mail: chekhun@onconet.kiev.ua
Abbreviation used: miRNAs — microRNAs.
Exp Oncol ����
���� 4�� �������
��4 Experimental Oncology ���� ��������� ���� ��ecem�er��
ducted �y Saito et al. [��] showed clearly the role of
epigenetic mechanisms in expression of mir-127 gene��
which is located within a CpG island on chromosome
14q��.�1. Additionally�� the inhi�ition of histone deacet-
ylase and the resulting rapid alterations in miRNA
levels in �reast cancer cells [��] further indicate the
importance of epigenetic mechanisms in regulation of
miRNA genes expression. On the other hand�� miRNAs
may �e involved in regulation of chromatin structure
�Figure��. In support of this hypothesis�� a recent pre-
diction of miRNA target genes in humans contained
various histone-modifying proteins�� including histone
methyltransferases�� methyl CpG-�inding proteins�� and
histone deacetylases [�4]. Recent finding �y Gross-
hans et al. [�4] that chromatin-remodeling factor is one
of let-7 predicted target genes in C. elegans provided
extra evidence to this hypothesis. In addition�� miRNAs
can affect chromatin structure indirectly �y regulating
proteins that involved in the maintenance of chromatin
organization. For instance�� miR-1��a involved in the
histone H� lysine � methylation and preservation of
heterochromatin via regulation of retino�lastoma-1
protein [��]. In any case�� the area of miRNAs/epigene-
tic changes relationships remains unexplored.
miRNAs As RegulAtoRs of diffeReNt
cellulAR pRocesses
miRNA genes represent only a small part �~�.5�
�%�� of the genome [7�� 17]�� �ut they regulate approxi-
mately �� to ��% of all human genes and there is an
average ��� predicted targets per miRNA [54�� 5���
���� �4]. Among these putative target-genes�� there is
a large group of genes involved in development�� cell
differentiation�� apoptosis�� transcriptional regulation��
and other physiological processes [4���� 1��� 5��� 51�� 5���
7��� 7��� ��]. Possi�ly�� not all predicted mRNAs are real
targets of corresponding miRNAs. However�� recent
report a�out altered expression of hundreds of mRNAs
in response to in vivo inhi�ition of miR-1�� supports
hypothesis of multiple targets for one miRNA [5�].
To date�� only a few miRNA targets have �een identi-
fied and confirmed experimentally thus clarifying the
mechanisms of their action. For example�� the let-7
family controls the timing of developmental processes
in C. elegans [1��17]�� and the involvement of miRNAs
in developmental processes has also �een shown in
Drosophila [�]. Several studied miRNAs are involved
in regulation of cell differentiation; thus�� miR-�1 in
Drosophila [�1] and miR-1��a in mice [��] control axial
patterning of the em�ryo. Brain-specific miR-1�4a and
miR-� affect neural differentiation in mouse em�ryo-
nic stem cells [57]. A complex system of interacting
miRNAs and transcription factors have �een found
to regulate cell fate determination in C. elegans [1���
���� 47�� ��] and Drosophila [�5]. In these models�� the
miRNAs and protein factors formed reciprocal negative
feed�ack loops allowing the existence of only one of
two sta�le states; the switch is gained �y mutual re-
figure. Biogenesis and cellular functions of miRNAs. Polymerase II transcri�es miRNA gene forming long hairpin-�earing primary
miRNA �pri-miRNA��. The hairpin structure is excised �y RNase III endonuclease �rosha�� and resulting pre-miRNA is transported
into cytoplasm �y Exportin-5 in a RAN-GTP dependent way. The cytoplasmic RNase III endonuclease �icer excises the top loop of
the miRNA giving RNA-RNA duplex. After unwinding�� one strand of the duplex is degraded�� and another strand is mature miRNA. It
can induce mRNA cleavage�� if complementarity to �´-untranslated regions of targets is perfect�� translational repression�� if comple-
mentarity is imperfect�� and transcriptional repression due to interactions with chromatin
Experimental Oncology ���� ��������� ���� ��ecem�er�� ��5���� ��������� ���� ��ecem�er�� ��5�ecem�er�� ��5�� ��5 ��5
pression of miRNA expression through corresponding
transcription factors.
A very intriguing pro�lem is miRNA patterns in stem
cells and their changes during differentiation. Generally��
stem cells possess a specific set of miRNAs which is
replaced during development [4��� ��]. A key charac-
teristic of stem cells is their capacity to divide for long
periods. In this respect�� stem cells are similar to cancer
cells�� which are also capa�le of escaping cell cycle ar-
rest. Therefore�� there is growing interest to elucidate
the mechanisms responsi�le for indicated properties.
Results of recent experiments suggest miRNA involve-
ment in stem cell self-renewal [���� �4]. Drosophila with
a null mutation of �icer-1�� which is required for miRNA
processing�� reduced �y ��% germline stem cell division
[�7]. It is known that the transition from G1 to S phases
of the cell cycle is negatively regulated �y �acapo ��ap����
an inhi�itor of cyclin-dependent kinase. In the mutant
Drosophila�� �ap was over-expressed�� possi�ly due to
a�sence of �ap-down-regulating miRNAs. Therefore��
miRNAs are required for germline stem cells to transit
the G1/S checkpoint �y repressing the G1/S inhi�itor
�ap. These results allow speculating that miRNAs could
have a similar role in cancer cells [�7].
In addition to important roles of miRNAs in regulation
of various cellular physiological pathways mentioned
a�ove�� a recent o�servation of targeting repetitive se-
quences�� such as Alu elements�� �y miRNAs indicates
a crucial role of miRNAs in defense of the mammalian
genome via silencing of foreign �NA sequences pre-
venting and maintaining sta�ility of the genome [�7].
miRNAs ANd cANceR
Taking into account an important role of miRNAs in
regulation of the key processes of cell life and death��
the involvement of microRNAome deregulation in di-
sease development�� including cancer�� can �e predicted.
Indeed�� recent studies showed a link �etween altered
miRNA patterns and cancer [1���1��� �5�� ���� �1�� 44]. Al-
tered miRNA patterns in tumor versus non-tumor cells
have �een found in chronic lymphocytic leukemia [1�]��
B-cell lymphomas [�7�� ���� 55��]�� Burkitt’s lymphoma
[7�]�� �reast cancer [45]�� lung cancer [4��� ���� �7]��
colorectal cancer [74]�� glio�lastoma [1�]�� follicular
thyroid carcinoma [�4]�� cholangiocarcinoma [7�]�� and
hepatocellular carcinoma [75]. Additionally�� detailed
studies reveal that more than half of miRNA genes are
located at sites in the human genome associated with
amplification�� deletion or translocation in cancer�� sug-
gesting direct relationship �etween miRNA a�normali-
ties and cancer pathogenesis [11�� 14�� �1�� ���� 1�1].
Generally�� there are two approaches linking
miRNAome deregulation to cancer in the context of
diagnosis and prognosis: �i�� comparison of glo�al
miRNA profiles in cancer and non-cancer tissues;
and�� �ii�� search for individual miRNAs that may have
diagnostic and prognostic significance in certain types
of cancer. For example�� chronic lymphocytic leukemia
is accompanied �y loss of miR-15a and miR-1�-1 lo-
cated in frequently deleted chromosomal region [1�];
in lung cancer�� the let-7 miRNA is down-regulated�� and
its reduced expression correlates with poor survival
of patients [��]; miR-155 is over-expressed in B-cell
lymphomas [�7�� 55].
miRNAs involved in cancer can have either pro- or
anti-tumorigenic action [5�]. Anti-tumorigenic�� or
tumor-suppressing miRNAs act as inhi�itors of cell
proliferation and stimulators of apoptosis. Contrarily��
group of miRNAs acting in the opposite direction �y
stimulating cell proliferation and inhi�iting of cell death
is termed “oncogenic miRNAs” [�5].
Ta�le summarizes availa�le information regarding
cancer-related miRNAs and their targets. Tumor-sup-
pressor miRNAs are frequently down-regulated or
deleted in cancer and�� respectively�� their targets are
over-expressed. These include transcription factors
and other regulatory proteins stimulating cell growth
and proliferation. Oncogene RAS is negatively regulated
�y let-7 miRNA�� which is down-regulated in human
lung cancer [4�]. Two mem�ers of BCL family�� BCL�
and BCL��� are targets of miR-15a/miR1�-1 and miR-
1�7�� respectively. Both miRNAs are often deleted or
down-regulated in leukemia and lymphomas [1��� �7]
and increased level of � and BCL� proteins suppresses
apoptosis and promotes cell proliferation [�4]. miR-14�
regulates extracellular signal-regulated kinase 5 �ERK5����
a MAP kinase that is activated �y growth factors and in-
volved in regulation of cell proliferation [7�].
Table. Selected tumor suppressor and oncogene miRNAs
miRNAs Targets Type of cancer References
Tumor suppressor miRNAs (downregulated or deleted in cancer)
miR-15a BCL2 B-cell chronic lymphocytic 8, 11, 13, 15,
24, 27
miR-16-1 BCL2 Adenomas, leukemia, lymphomas,
pituitary
let-7 RAS lung cancer 2, 46, 90, 97
miR-143 ERK5 breast, colon and lung cancer 3, 45, 74, 97
miR-145 ?
miR-127 BCL6 Bladder, colon and prostate cancer 82
Oncogene miRNAs (upregulated in cancer)
miR-155 ? B-cell lymphomas, Burkitt’s lymphoma,
breast, colon, lung, thyroid cancer
27, 45, 55,
73, 91, 92, 97
The miR-17-
92 cluster
E2F1
PTEN
TGFBR2
lymphomas, breast, colon, lung,
pancreas and prostate cancer
38, 39, 92
miR-21 PTEN breast, colon, glioblastoma, liver, lung,
pancreas, prostate, stomach cancer
18, 5, 59,
72, 92, 97
miR-372 LATS2 testicular germ cell cancer 93
miR-373 LATS2
miR-106a RB1 colon, liver, lung, pancreas, pros-
tate cancer
59, 92, 97
miR-9 CDH1 breast cancer 45
Both tumor suppressor and oncogene miRNAs
The miR-17-92 cluster:
miR-17-5p E2F1 77
miR-20a E2F1 77
miR-17-5p AIB1 breast cancer 41
miR-130a MAFB 29
Over-expression of oncogenic miRNAs negatively
regulates tumor-suppressor genes including retino-
�lastoma 1 �RB1; a regulator of the cell cycle���� large
tumor suppressor homolog � �LATS�; an inhi�itor
of cyclin-dependent kinase ����� E-cadherin �C�H1;
involved in cell-cell adhesion���� transforming growth
factor-β receptor II �TGFBR���. PTEN �phosphatase
and tensin homolog���� a target of two miRNAs�� miR-�1
and the miR-17-�� cluster�� encodes a phosphatase
��� Experimental Oncology ���� ��������� ���� ��ecem�er��
that inhi�its PI-� kinase pathway; the last promotes
cell survival/growth [7�].
Several target genes have �een found for the miR-
17-�� cluster that includes seven miRNAs: miRs-17-5p��
-17-�p�� -1��� -1�a�� -1���� -���� and -��. The miR-17-��
cluster is located on human chromosome 1�q�1�� a re-
gion that is easily amplified in several types of cancer
including lymphomas [��]. A remarka�le feature of this
cluster is its capacity to function as �oth oncogene and
tumor suppressor with the result depending on the real
situation in the cell. Using a mouse model of c-Myc-in-
duced B-cell lymphoma�� He et al. [��] found that en-
forced expression of the miR-17-�� cluster dramatically
accelerates disease development with a simultaneous
decrease in apoptosis�� indicating that these miRNAs
act primarily �y suppressing cell death.
O’�onnell et al. [77] showed that c-Myc trans-
criptionally regulated the miR-17-�� expression. In
addition�� two miRNAs in this cluster�� miR-17-5p and
miR-���� regulated the transcription factor E�F1�� func-
tioning �oth as oncogene and tumor suppressor�� at
posttranscriptional level. E�F1 and c-Myc are known to
induce each other’s expression. In the a�sence of other
controls�� this can set up a positive feed�ack loop lead-
ing to over-expression of �oth genes with destructive
consequences for normal cell-cycle regulation. At high
level of expression�� E�F1 favors apoptosis induction
through the ARF-p5� pathway [�5]. Therefore�� damp-
ening of translation efficiency �y the miR-17-�� cluster
might shift the E�F1 action to enhanced proliferation.
Generally�� the loop c-Myc/miR-17-5p-miR-��a/E�F1
ensures precise control �y c-Myc of target gene expres-
sion with simultaneous activation of their transcription
and restriction of their translation. Therefore�� this cluster
reveals�� on one hand�� oncogenic action stimulating cell
proliferation and�� on the other hand�� suppressor activity
via negative regulatory feed-�ack loop c-Myc/miR-
17-5p-miR-��a/E�F1 [5�]. Recently one more tumor
suppressor action of this cluster has �een found: in
�reast cancer�� miR-17-5p repressed translation of the
oncogene AIB1 �“amplified in �reast cancer 1”�� [41].
Another miRNA�� miR-1��a�� also exhi�its �oth tumor
suppressor and oncogene action. This miRNA targets
the transcription factor MAFB that plays a dual role in
carcinogenesis acting as �oth oncogene and tumor
suppressor [7�].
�espite the fact of the esta�lished link �etween
miRNAs deregulation and cancer�� very little is known
regarding miRNA changes during early stages of
carcinogenesis. He et al. [4�] showed that in non-tu-
mor tissues adjacent to papillary thyroid carcinoma��
miR-��1�� highly expressed in tumor cells�� was also
up-regulated — pro�a�ly reflecting an early event in
pathogenesis. In hepatocellular carcinomas�� miR-��
and miR-�1 expression was enhanced in preneo-
plastic nodules compared to normal liver�� and further
increased in tumors [5�]. First signs of miRNA altera-
tions during carcinogenesis require extensive studies
to determine the key miRNAs that could reflect early
events in cancer development.
coNclusioNs ANd peRspectives
�iscovered recently�� miRNAs have �een unexpected-
ly recognized as new glo�al regulators of gene
expression that control the key processes in the
cell — growth�� development�� apoptosis. miRNAs are
a�le to simultaneously regulate many mRNAs forming
regulatory network that can act in a flexi�le manner for
precise and quick effects on gene expression.
A prominent role of oncogene and tumor-suppres-
sor miRNAs in cancer renders them as a useful tool for
diagnostic and prognostic purposes [���� �7]. miRNA
profiles are very informative�� reflecting the develop-
mental progress and differentiation state of tumors;
moreover�� they �etter than mRNA profiles distinguish
cancer and non-cancer tissues [�5�� ��] and in some
cases are changed already at early stages of cancer
development prior clinical signatures of disease [11��
75]. Altered expression of specific miRNAs has �een
found in a diversity of cancers giving a promising per-
spective to use such miRNAs as targets for anticancer
therapy. One approach may �e treatment with precur-
sors of tumor suppressor miRNAs that are often down-
regulated in cancer. For example�� the let-7 miRNA may
�e useful in treatment of lung cancer [�5]; as demon-
strated on human cancer cells�� transfect ion with its
precursor suppressed proliferation and simultaneously
decreased RAS and c-MYC proteins [�]. In case of
oncogene miRNAs�� an effective approach might �e
using antisense olidonucleotides to inhi�it respective
miRNAs due to competition with mRNAs for �inding
miRNAs [���� ��]. Antisense therapy has �een success-
fully tested in vitro [4��� 71]�� and chemically modified
anti-miRNAs termed ‘antagomirs’ could inhi�it specific
miRNAs and su�sequently upregulated their targets
in vivo [5�]. However�� �efore wide practical use�� a
num�er of questions should �e clarified. They include
miRNA roles in cellular pathways and mechanisms of
regulation of their expression in general and search
and confirmation critical miRNAs involved in the de-
velopment of given type of cancer in particular. Finally��
a fully unexplored area is effects of anticancer therapy
on the miRNA expression. Some data indicate that
such treatment can alter miRNA profiles in cancer cells
and result in resistance to anticancer drugs [�1�� 7�].
Therefore�� �oth fundamental and clinic-related studies
are needed to �etter understand roles of miRNAs in
normal and cancer cells and modulate cellular growth��
proliferation and meta�olism using miRNAs.
AckNowledgemeNts
This work was supported in part �y a Postgraduate
Research Program administered �y the Oak Ridge
Institute for Science and Education �TB��.
RefeReNces
1. Abbott AL, Alvarez-Saavedra E, Miska EA, Lau NC,
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МикроРНК в НоРМальНых и опухолевых КлетКах:
Новый Класс РегулятоРов эКспРессии геНов
Микро РНК (miRNAs) �� ��о ������ ���ко�ир���и�� РНК, ������и��о р�����ир���и�� �к��р����и� ����о� �� �о���р���кри��ио�-miRNAs) �� ��о ������ ���ко�ир���и�� РНК, ������и��о р�����ир���и�� �к��р����и� ����о� �� �о���р���кри��ио�-) �� ��о ������ ���ко�ир���и�� РНК, ������и��о р�����ир���и�� �к��р����и� ����о� �� �о���р���кри��ио�-
�о� �ро���� и �ри�и����и�� �ч���и�� � р�з�и�ии, �ифф��р����иро�к��, �ро�иф��р��ии и ��о��оз�� к����ок, � ��кж�� ���о��я��и��
��ж��� ро�ь � о��хо����о� �ро�������. В обзор�� об��ж���� био������з miRNA, ф��к�ии ��их �о���к�� � �ор���ь��х к����к�х, из-miRNA, ф��к�ии ��их �о���к�� � �ор���ь��х к����к�х, из-, ф��к�ии ��их �о���к�� � �ор���ь��х к����к�х, из-
�������ия ��бор� miRNA � о��хо�����х к����к�х и ро�ь �ро�и�оо��хо�����х и о�ко������х miRNAs � о��хо����о�� �ро�р����ии.miRNA � о��хо�����х к����к�х и ро�ь �ро�и�оо��хо�����х и о�ко������х miRNAs � о��хо����о�� �ро�р����ии. � о��хо�����х к����к�х и ро�ь �ро�и�оо��хо�����х и о�ко������х miRNAs � о��хо����о�� �ро�р����ии.miRNAs � о��хо����о�� �ро�р����ии. � о��хо����о�� �ро�р����ии.
Ключевые слова: �икроРНК, р�к, о�ко����, о��хо������� ���р����ор.
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