Identifying microRNAs regulating B7-H3 in breast cancer: The clinical impact of microRNA-29c

M.K. Nygren, C. Tekle, V.A. Ingebrigtsen, Rami Mäkelä, M. Krohn, M.R. Aure, C.E. Nunes-Xavier, Merja Perälä, T. Tramm, J. Alsner, J. Overgaard, J.M. Nesland, E. Borgen, A.-L. Børresen-Dale, Ø. Fodstad, K.K. Sahlberg, S.-K. Leivonen (Corresponding Author)

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Abstract

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
Original languageEnglish
Pages (from-to)2072-2080
JournalBritish Journal of Cancer
Volume110
Issue number8
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

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MicroRNAs
Breast Neoplasms
3' Untranslated Regions
Down-Regulation
Western Blotting
Neoplasms
Protein Array Analysis
Proteins
Luciferases
Publications
Neoplasm Metastasis
Cell Line
Survival

Cite this

Nygren, M. K., Tekle, C., Ingebrigtsen, V. A., Mäkelä, R., Krohn, M., Aure, M. R., ... Leivonen, S-K. (2014). Identifying microRNAs regulating B7-H3 in breast cancer: The clinical impact of microRNA-29c. British Journal of Cancer, 110(8), 2072-2080. https://doi.org/10.1038/bjc.2014.113
Nygren, M.K. ; Tekle, C. ; Ingebrigtsen, V.A. ; Mäkelä, Rami ; Krohn, M. ; Aure, M.R. ; Nunes-Xavier, C.E. ; Perälä, Merja ; Tramm, T. ; Alsner, J. ; Overgaard, J. ; Nesland, J.M. ; Borgen, E. ; Børresen-Dale, A.-L. ; Fodstad, Ø. ; Sahlberg, K.K. ; Leivonen, S.-K. / Identifying microRNAs regulating B7-H3 in breast cancer : The clinical impact of microRNA-29c. In: British Journal of Cancer. 2014 ; Vol. 110, No. 8. pp. 2072-2080.
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title = "Identifying microRNAs regulating B7-H3 in breast cancer: The clinical impact of microRNA-29c",
abstract = "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",
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Nygren, MK, Tekle, C, Ingebrigtsen, VA, Mäkelä, R, Krohn, M, Aure, MR, Nunes-Xavier, CE, Perälä, M, Tramm, T, Alsner, J, Overgaard, J, Nesland, JM, Borgen, E, Børresen-Dale, A-L, Fodstad, Ø, Sahlberg, KK & Leivonen, S-K 2014, 'Identifying microRNAs regulating B7-H3 in breast cancer: The clinical impact of microRNA-29c', British Journal of Cancer, vol. 110, no. 8, pp. 2072-2080. https://doi.org/10.1038/bjc.2014.113

Identifying microRNAs regulating B7-H3 in breast cancer : The clinical impact of microRNA-29c. / Nygren, M.K.; Tekle, C.; Ingebrigtsen, V.A.; Mäkelä, Rami; Krohn, M.; Aure, M.R.; Nunes-Xavier, C.E.; Perälä, Merja; Tramm, T.; Alsner, J.; Overgaard, J.; Nesland, J.M.; Borgen, E.; Børresen-Dale, A.-L.; Fodstad, Ø.; Sahlberg, K.K.; Leivonen, S.-K. (Corresponding Author).

In: British Journal of Cancer, Vol. 110, No. 8, 2014, p. 2072-2080.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 110

SP - 2072

EP - 2080

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 8

ER -