TY - JOUR
T1 - Identifying microRNAs regulating B7-H3 in breast cancer
T2 - The clinical impact of microRNA-29c
AU - Nygren, M.K.
AU - Tekle, C.
AU - Ingebrigtsen, V.A.
AU - Mäkelä, Rami
AU - Krohn, M.
AU - Aure, M.R.
AU - Nunes-Xavier, C.E.
AU - Perälä, Merja
AU - Tramm, T.
AU - Alsner, J.
AU - Overgaard, J.
AU - Nesland, J.M.
AU - Borgen, E.
AU - Børresen-Dale, A.-L.
AU - Fodstad, Ø.
AU - Sahlberg, K.K.
AU - Leivonen, S.-K.
PY - 2014
Y1 - 2014
N2 - Background:B7-H3, an immunoregulatory protein, is
overexpressed in several cancers and is often associated
with metastasis and poor prognosis. Here, our aim was to
identify microRNAs (miRNAs) regulating B7-H3 and assess
their potential prognostic implications in breast cancer.
Methods:MicroRNAs targeting B7-H3 were identified by
transfecting two breast cancer cell lines with a library
of 810 miRNA mimics and quantifying changes of B7-H3
protein levels using protein lysate microarrays. For
validations we used western immunoblotting and 3'-UTR
luciferase assays. Clinical significance of the miRNAs
was assayed by analysing whether their expression levels
correlated with outcome in two cohorts of breast cancer
patients (142 and 81 patients). Results:We identified
nearly 50 miRNAs that downregulated B7-H3 protein levels.
Western immunoblotting validated the impact of the 20
most effective miRNAs. Thirteen miRNAs (miR-214,
miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*,
miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and
miR-593) targeted B7-H3 directly by binding to its 3'-UTR
region. Finally, high expression of miR-29c was
associated with a significant reduced risk of dying from
breast cancer in both cohorts. Conclusions:We identified
miRNAs efficiently downregulating B7-H3 expression. The
expression of miR-29c correlated with survival in breast
cancer patients, suggesting a tumour suppressive role for
this miRNA.British Journal of Cancer advance online
publication, 27 February 2014; doi:10.1038/bjc.2014.113
www.bjcancer.com
AB - Background:B7-H3, an immunoregulatory protein, is
overexpressed in several cancers and is often associated
with metastasis and poor prognosis. Here, our aim was to
identify microRNAs (miRNAs) regulating B7-H3 and assess
their potential prognostic implications in breast cancer.
Methods:MicroRNAs targeting B7-H3 were identified by
transfecting two breast cancer cell lines with a library
of 810 miRNA mimics and quantifying changes of B7-H3
protein levels using protein lysate microarrays. For
validations we used western immunoblotting and 3'-UTR
luciferase assays. Clinical significance of the miRNAs
was assayed by analysing whether their expression levels
correlated with outcome in two cohorts of breast cancer
patients (142 and 81 patients). Results:We identified
nearly 50 miRNAs that downregulated B7-H3 protein levels.
Western immunoblotting validated the impact of the 20
most effective miRNAs. Thirteen miRNAs (miR-214,
miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*,
miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and
miR-593) targeted B7-H3 directly by binding to its 3'-UTR
region. Finally, high expression of miR-29c was
associated with a significant reduced risk of dying from
breast cancer in both cohorts. Conclusions:We identified
miRNAs efficiently downregulating B7-H3 expression. The
expression of miR-29c correlated with survival in breast
cancer patients, suggesting a tumour suppressive role for
this miRNA.British Journal of Cancer advance online
publication, 27 February 2014; doi:10.1038/bjc.2014.113
www.bjcancer.com
U2 - 10.1038/bjc.2014.113
DO - 10.1038/bjc.2014.113
M3 - Article
SN - 0007-0920
VL - 110
SP - 2072
EP - 2080
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -
