Kleemann, M.* ; Bereuther, J.* ; Fischer, S.* ; Marquart, K.* ; Hänle, S.* ; Unger, K. ; Jendrossek, V.* ; Riedel, C.U.* ; Handrick, R.* ; Otte, K.*
Investigation on tissue specific effects of pro-apoptotic micro RNAs revealed miR-147b as a potential biomarker in ovarian cancer prognosis.
Oncotarget 8, 18773-18791 (2017)
The development and progression of cancer can be ascribed to imbalances in gene regulation leading to aberrant cellular behavior. The loss of micro RNAs (miRNAs) exhibiting tumor-suppressive function has been demonstrated to be often causative for uncontrolled cell proliferation, migration or tissue infiltration. The installation of de novo tumor suppressive function by using pro-apoptotic miRNAs might be a promising therapeutic approach. In addition, there is a great demand for novel biomarkers for the prognosis of cancer, which prompted us to transfer a high content miRNA screening initially performed to identify bioprocess relevant miRNAs in Chinese hamster ovary (CHO) cells to human cancer cell lines . Analysis of screened miRNAs exhibiting strongest pro-apoptotic effects discovered globally and cross-species active candidates. The recovery rate of apoptosis inducing miRNAs was highest in the human ovarian carcinoma cell line SKOV3. Focusing on ovarian cell lines miR-1912, miR-147b and miR-3073a showed significant apoptosis induction in cell lines with different genetic background (SKOV3p53null, OVCAR3p53R248Q, TOV21G, TOV112Dp53R175H, A2780, A2780-cisp53K351N) alone and additive effects in combination with carboplatin. While expression analysis revealed a low endogenous expression of miR-1912 and miR-147b in SKOV3, miRNA expression was highly upregulated upon apoptosis induction using chemotherapeutics. Ectopic introduction of these miRNAs lead to enhanced activation of caspase-dependent death signaling and an induction of the pro-apoptotic proteins Bak1 and Bax and a reduced expression of Bcl2 and Bcl-xL. Finally, analysis of The Cancer Genome Atlas data revealed the expression of hsa-miR-147b-5p to show a positive influence on the median survival of ovarian cancer patients.
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Article: Journal article
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Scientific Article
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Keywords
Apoptosis ; Biomarker ; Mir-147b ; Ovarian Cancer ; Prognosis
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Language
english
Publication Year
2017
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2017
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1949-2553
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1949-2553
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Volume: 8,
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Pages: 18773-18791
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Impact Journals LLC
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
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Radiation Sciences
PSP Element(s)
G-501000-001
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Erfassungsdatum
2017-05-22