The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1.
microRNAs (miRNAs) are small molecules that regulate gene expression posttranscriptionally. In a previous study, we identified miR-96 to be upregulated in prostate cancer specimens in comparison to normal adjacent tissue and to be an independent marker of biochemical relapse in a multivariate predic...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3834337?pdf=render |
| _version_ | 1818113077346828288 |
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| author | Annika Fendler Monika Jung Carsten Stephan Andreas Erbersdobler Klaus Jung George M Yousef |
| author_facet | Annika Fendler Monika Jung Carsten Stephan Andreas Erbersdobler Klaus Jung George M Yousef |
| author_sort | Annika Fendler |
| collection | DOAJ |
| description | microRNAs (miRNAs) are small molecules that regulate gene expression posttranscriptionally. In a previous study, we identified miR-96 to be upregulated in prostate cancer specimens in comparison to normal adjacent tissue and to be an independent marker of biochemical relapse in a multivariate prediction model. Therefore, we investigated the functional role of miR-96 in prostate carcinogenesis. LNCaP and DU145 prostate cancer cells were transiently transfected with miR-96 precursors and phenotypic changes were analyzed. The miR-96 increased proliferation and impaired apoptosis induced by camptothecine in these cells. In silico target prediction analysis identified FOXO1 as potential pro-apoptotic miR-96 target. miR-96 was able to bind to both bindings sites in the FOXO1 3' UTR in a luciferase reporter gene assay. Overexpression of miR-96 in LNCaP cells resulted in a reduced FOXO1 expression. Overexpression of FOXO1 induced a strong apoptotic phenotype that was partially rescued by coexpression of miR-96. RT-qPCR and immunohistochemistry of 69 prostate cancer specimens revealed a downregulation of FOXO1 and an inverse correlation of miR-96 and FOXO1 protein expression. In conclusion, we show that miR-96 can regulate apoptosis in prostate cancer, by inhibiting the FOXO1 transcription factor. |
| first_indexed | 2024-12-11T03:29:06Z |
| format | Article |
| id | doaj.art-b40cedbc9dc14acaa6f743f99bf2b604 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T03:29:06Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b40cedbc9dc14acaa6f743f99bf2b6042022-12-22T01:22:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8080710.1371/journal.pone.0080807The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1.Annika FendlerMonika JungCarsten StephanAndreas ErbersdoblerKlaus JungGeorge M YousefmicroRNAs (miRNAs) are small molecules that regulate gene expression posttranscriptionally. In a previous study, we identified miR-96 to be upregulated in prostate cancer specimens in comparison to normal adjacent tissue and to be an independent marker of biochemical relapse in a multivariate prediction model. Therefore, we investigated the functional role of miR-96 in prostate carcinogenesis. LNCaP and DU145 prostate cancer cells were transiently transfected with miR-96 precursors and phenotypic changes were analyzed. The miR-96 increased proliferation and impaired apoptosis induced by camptothecine in these cells. In silico target prediction analysis identified FOXO1 as potential pro-apoptotic miR-96 target. miR-96 was able to bind to both bindings sites in the FOXO1 3' UTR in a luciferase reporter gene assay. Overexpression of miR-96 in LNCaP cells resulted in a reduced FOXO1 expression. Overexpression of FOXO1 induced a strong apoptotic phenotype that was partially rescued by coexpression of miR-96. RT-qPCR and immunohistochemistry of 69 prostate cancer specimens revealed a downregulation of FOXO1 and an inverse correlation of miR-96 and FOXO1 protein expression. In conclusion, we show that miR-96 can regulate apoptosis in prostate cancer, by inhibiting the FOXO1 transcription factor.http://europepmc.org/articles/PMC3834337?pdf=render |
| spellingShingle | Annika Fendler Monika Jung Carsten Stephan Andreas Erbersdobler Klaus Jung George M Yousef The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. PLoS ONE |
| title | The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. |
| title_full | The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. |
| title_fullStr | The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. |
| title_full_unstemmed | The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. |
| title_short | The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. |
| title_sort | antiapoptotic function of mir 96 in prostate cancer by inhibition of foxo1 |
| url | http://europepmc.org/articles/PMC3834337?pdf=render |
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