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Kaposi's sarcoma-associated herpesvirus microRNA single-nucleotide polymorphisms identified in clinical samples can affect microRNA processing, level of expression, and silencing activity.
[primary effusion lymphoma]
Kaposi
's
sarcoma
-associated
herpesvirus
(
KSHV
)
encodes
12
pre-micro
RNAs
that
can
produce
25
KSHV
mature
microRNAs
.
We
previously
reported
single
-nucleotide
polymorphisms
(
SNPs
)
in
KSHV-encoded
pre-micro
RNA
and
mature
microRNA
sequences
from
clinical
samples
(
V
.
Marshall
et
al
.
,
J
.
Infect
.
Dis
.
,
195
:
645
-
659
,
2007
)
.
To
determine
whether
microRNA
SNPs
affect
pre-micro
RNA
processing
and
,
ultimately
,
mature
microRNA
expression
levels
,
we
performed
a
detailed
comparative
analysis
of
(
i
)
mature
microRNA
expression
levels
,
(
ii
)
in
vitro
Drosha
/
Dicer
processing
,
and
(
iii
)
RNA-induced
silencing
complex
-dependent
targeting
of
wild-
type
(
wt
)
and
variant
microRNA
genes
.
Expression
of
pairs
of
wt
and
variant
pre-micro
RNAs
from
retroviral
vectors
and
measurement
of
KSHV
mature
microRNA
expression
by
real-time
reverse
transcription-
PCR
(
RT-PCR
)
revealed
differential
expression
levels
that
correlated
with
the
presence
of
specific
sequence
polymorphisms
.
Measurement
of
KSHV
mature
microRNA
expression
in
a
panel
of
primary
effusion
lymphoma
cell
lines
by
real-time
RT-PCR
recapitulated
some
observed
expression
differences
but
suggested
a
more
complex
relationship
between
sequence
differences
and
expression
of
mature
microRNA
.
Furthermore
,
in
vitro
maturation
assays
demonstrated
significant
SNP-associated
changes
in
Drosha
/
DGCR
8
and
/
or
Dicer
processing
.
These
data
demonstrate
that
SNPs
within
KSHV-encoded
pre-micro
RNAs
are
associated
with
differential
microRNA
expression
levels
.
Given
the
multiple
reports
on
the
involvement
of
microRNAs
in
cancer
,
the
biological
significance
of
these
phenotypic
and
genotypic
variants
merits
further
studies
in
patients
with
KSHV-associated
malignancies
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated