The role of circulating miRNAs in multiple myeloma
Zhang J, Xiao XJ, Liu J. The role of circulating miRNAs in multiple myeloma. Sci China Life Sci
The role of circulating miRNAs in multiple myeloma
ZHANG Ji 0 1
XIAO XiaoJuan 0
LIU Jing 0
0 State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University , Changsha 410078 , China
1 Department of Hematology, The First Affiliated Hospital, University of South China , Hengyang 421001 , China
Multiple myeloma (MM) is a common malignant hematological disease. Dysregulation of microRNAs (miRNAs) in MM cells and bone marrow microenviroment has important impacts on the initiation and progression of MM and drug resistance in MM cells. Recently, it was reported that MM patient serum and plasma contained sufficiently stable miRNA signatures, and circulating miRNAs could be identified and measured accurately from body fluid. Compared to conventional diagnostic parameters, the circulating miRNA profile is appropriate for the diagnosis of MM and estimates patient progression and therapeutic outcome with higher specificity and sensitivity. In this review, we mainly focus on the potential of circulating miRNAs as diagnostic, prognostic, and predictive biomarkers for MM and summarize the general strategies and methodologies for identification and measurement of circulating miRNAs in various cancers. Furthermore, we discuss the correlation between circulating miRNAs and the cytogenetic abnormalities and biochemical parameters assessed in multiple myeloma.
miRNA; multiple myeloma; biomarker; diagnosis
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Citation:
Multiple myeloma (MM) accounts for approximately 13%
of all hematologic malignancies and 1% of all
malignancies [
1,2
]. MM is a clonal B-cell malignancy
characterized by the expansion of clonal plasma cells in the bone
marrow, accompanied by abnormal accumulation of
monoclonal antibodies [3,4]. Typically, MM evolves from a
premalignant condition known as monoclonal gammopathy
of undetermined significance (MGUS). The incidence of
MGUS is approximately 3% in the general population 50
years of age or older, and approximately 1% of MGUS
patients develop into MM each year [1]. Compared to MM,
MGUS is characterized by a lower concentration of serum
monoclonal antibody, less bone marrow plasmacytosis and
a lack of organ damage, including hypercalcemia, renal
impairment, anemia and bone lesions. Currently, there are no
specific tests for distinguishing between these two
conditions and estimating the risk of progression from MGUS to
MM. Additionally, no current strategies exist to prevent the
progression from MGUS to MM; therefore, novel
biomarker which may predict progression is urgently needed in
MGUS patients.
miRNAs are an abundant class of regulatory noncoding
single-stranded RNA molecules approximately 20–23
nucleotides long. In general, miRNAs bind with imperfect
complementarity to the 3′-untranslated region (3′-UTR
(untranslated regions)) of a specific target mRNA to
promote its degradation and/or inhibit its translation [5]. Many
miRNAs display regulatory roles in all major biological
processes, including cell motility, differentiation,
proliferation and apoptosis [6,7]. Aberrant miRNA expression
profiles are frequently discovered during the initiation and
progression of cancers, including early or advanced disease
stages, response, remission and relapse. Recently, it has
been demonstrated that miRNAs are secreted into body
fluids, including serum and plasma, and can maintain stability
while freely circulating in the bloodstream.
© The Author(s) 2015. This article is published with open access at link.springer.com
miRNAs and MM
As growing research has indicated that miRNAs played
important roles in the occurrence, development, recurrence
and drug resistance of MM, miRNA signatures may serve as
potential biomarkers for myeloma diagnosis, prognosis, and
response to treatment. For example, hemizygous and/or
homozygous chromosomal deletion at the 13q14 locus in
MM patients can result in the loss of or reduction in
expression of miR-15 and miR-16, which is correlated with
tumorigenesis and the development of MM [8,9]. Pichiorri et
al. [10] first described comprehensive global miRNA
expression profiling of MM, MGUS and normal plasma cells,
which indicated that MM miRNA signatures modulated the
expression of proteins critical to myeloma pathogenesis. In
2010, Gutierrez et al. [11] investigated the association
between miRNA expression profiles and their corresponding
target genes and found that the downregulation of several
miRNAs resulted in overexpression of cyclin D2 (CCND2)
in MM. These authors demonstrated for the first time that
miRNA expression patterns in MM were associated with
genetic abnormalities. Yyusnita et al. [12] revealed that
several miRNAs, including downregulated let-7c and
m i R-1 6 a n d u p r eg u la t e d m i R-4 4 9 , m i R-1 8 1 a a n d
miR-181b, exhibited similar expression patterns in
peripheral blood compared to data obtained from bone marrow
aspirates of MM (...truncated)