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FC > 2 FC > 2
MB vs. CTR common
(CSF) enriched
5
n = 22 CM
n = 128

HSID Nam ID FC FC FC FC
FC
FC
ID
FC
FC
Namee
HSID
CM vsC (D283) CM vsC (D341)vsC (D283) CM vsC (D341) CMvsC (DAOY)vsC (DAOY) MB
CM
MB vsCTRvsCTR
CM
6.7878
MIMAT0004762MIMAT0004762 6. 18.4618.46 10.7810.78 2.012.01
hs_1346hs_1346 hsa-miR-486-3p
hs_1517hs_1517 hsa-miR-572 MIMAT0003237MIMAT0003237 6. 8.768.76 3.4747 2.532.53
3.
6.1010
hs_0978hs_0978 hsa-miR-4476 MIMAT0019003MIMAT0019003 5.0404 4.734.73 2.7979 2.542.54
2.
5.
hs_1566hs_1566 hsa-miR-615-5p MIMAT0004804MIMAT0004804 2.9292 4.254.25 2.1616 2.042.04
2.
2.
2.5151
hs_0775hs_0775 hsa-miR-3918 MIMAT0018192MIMAT0018192 2. 2.662.66 2. 2.112.11
2.0808
a
FC > 2
FC > 2
MR vs. non-
MB vs. CTR
4
MR
(CSF)
(CM)
n = 22
n = 38
FC
ID
Name
FC
HSI Name ID FC FC
HSIDD
MB vs CTRvs CTR
A MB
A vs NAvs NA
h
10.58
MI
2.63
h
hs_0152s_0152 hsa-miR-1290sa-miR-1290 MIMAT0005880MAT0005880 10.58 2.63
2.57
2.08
hsa-miR-125a-3p-miR-125a-3p
hs_0103
MI
hs_0103 hsa MIMAT0004602MAT0004602 2.57 2.08
2.15
2.57
h hs_0160s_0160 h hsa-miR-1298sa-miR-1298 MIMAT0005800MAT0005800 2.57 2.15
MI
b h hs_0106s_0106 hsa-miR-125b-1*sa-miR-125b-1* MIMAT0004592IMAT0004592 2.33 2.18
h
M
2.33
2.18
Figure 5: MiRNAs commonly enriched in CM of MB cell lines, and in CSF sample. (a) Venn diagram and table presenting 5 miRNAs commonly upregulated
in CM of 3 MB cell lines and in CSF from MB patients compared to CTR; (b) Venn diagram and table representing 4 miRNAs commonly upregulated in CSF
samples from MB patients and over-represented in CM of the MR cell lines D341, D283. CM: Culture-medium; MB: Medulloblastoma; CSF: Cerebral spinal
fl uid; MR: Metastasis related; FC: Fold change; CTR: Control; MiRNAs: MicroRNA
used in most diagnostic labs). Importantly, we could spectra in CM and those expressed intracellularly was
detect ex-miRNAs by qRT-PCR in CM of as few as observed. Since deregulated miRNA expression is an
100-500 MB cells [Figure 8b], recommending qRT-PCR early event in tumorigenesis, measuring miRNA levels
for the development of non-invasive detection of in CSF may also be useful for early detection, which
metastasis-predicting markers for MB. can contribute greatly to the success of treatment. [28]
Therefore, in order to use ex-miRNAs as biomarkers
Discussion for MB, it is important to establish a signature capable
Aberrant expression of ex-miRNA circulating in of differentiating disease from healthy states. Our
CSF of certain brain tumor patients has recently pilot microarray screening identifi ed 86 miRNAs
been reported to be cancer biomarkers and potential exclusively detected in CSF of MB patients but not
regulators of the disease. [7,8] However, the existence and in control CSF from patients with no brain tumor. We
role of ex-miRNAs in MB extracellular environment also identifi ed 268 miRNAs that are over-represented
are unknown. Therefore, better understanding of and interestingly, only 6 miRNAs under-represented in
ex-miRNA secretion and function in MB seems crucial MB-CSF compared with control CSF. These fi ndings
for the development of novel insights for its diagnosis could be of great signifi cance, providing the correlation
and prognosis. This study aimed to identify key between expression levels of these miRNAs in CSF of
miRNAs in culture medium of 3 cell lines, representing MB patients and their disease states can be established
different MB subtypes. Our results identifi ed a in future studies.
signifi cant number (1,347) of hitherto unrecognized Tumor cell-derived ex-miRNAs are reported to be
new miRNAs commonly expressed in CM of the 3 pro-tumorigenic. [29] Ex-miRNAs can transfer their
cell lines. A signifi cant concordance of ex-miRNA oncogenic activity to recipient target cells to infl uence
72 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦