A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression
Background: Epigenetic abnormalities are increasingly observed in multiple malignancies, including epithelial ovarian cancer (EOC), and their effects can be significantly counteracted by tumor-suppressor microRNAs, namely epi-miRNAs. Here, we investigated the role of miR-29b, a well-established epi-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/447926 |
| _version_ | 1819101705012248576 |
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| author | Yue Teng Xiaohang Zuo Meng Hou Yan Zhang Chen Li Wenjuan Luo Xu Li |
| author_facet | Yue Teng Xiaohang Zuo Meng Hou Yan Zhang Chen Li Wenjuan Luo Xu Li |
| author_sort | Yue Teng |
| collection | DOAJ |
| description | Background: Epigenetic abnormalities are increasingly observed in multiple malignancies, including epithelial ovarian cancer (EOC), and their effects can be significantly counteracted by tumor-suppressor microRNAs, namely epi-miRNAs. Here, we investigated the role of miR-29b, a well-established epi-miRNA, in the DNA methylation regulation of EOC cells. Methods: The correlation between miR-29b and DNMT3A/3B expression was evaluated by RT-qPCR, western blotting and immunohistochemical analysis. The functional roles of miR-29b and DNMT3A/3B were tested by anti-miRs and microRNA precursors. A luciferase reporter assay was employed to detect the direct binding of miR-29b to DNMT3A/3B 3′ UTRs. Co-IP was utilized for investigating Id-1 binding activity. Results: miR-29b was negatively correlated with DNMT3A/3B expression at the cellular/histological levels. miR-29b silencing was correlated with increased DNMT3A/3B levels, whereasmiR-29b over-expression caused DNMT3A/3B down-regulation. Luciferase reporter assays confirmed that the miR-29b-mediated downregulation of DNMT3A/3Boccurred through the direct targeting of theirmRNAs'3'-UTRs,whereasBGS assays found that DNMT3A/3B knockdown increased miR-29b expression via CpG island promoter hypomethylation, thus suggesting a crucial crosstalk betweenmiR-29b and DNMT3A/3B via a double-negative feedback loop. Co-IP assay confirmed direct binding between DNMT3A and Id-1. Conclusion: Taken together, our study sheds light on a novel epigenetic circuitry regulating EOC progression and may provide novel options for miR-29b-based epi-therapeutic approaches for future EOC treatment. |
| first_indexed | 2024-12-22T01:22:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T01:22:54Z |
| publishDate | 2016-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-ada292a1926a48debbc8e117588d9ced2022-12-21T18:43:42ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-11-013962341235210.1159/000447926447926A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer ProgressionYue TengXiaohang ZuoMeng HouYan ZhangChen LiWenjuan LuoXu LiBackground: Epigenetic abnormalities are increasingly observed in multiple malignancies, including epithelial ovarian cancer (EOC), and their effects can be significantly counteracted by tumor-suppressor microRNAs, namely epi-miRNAs. Here, we investigated the role of miR-29b, a well-established epi-miRNA, in the DNA methylation regulation of EOC cells. Methods: The correlation between miR-29b and DNMT3A/3B expression was evaluated by RT-qPCR, western blotting and immunohistochemical analysis. The functional roles of miR-29b and DNMT3A/3B were tested by anti-miRs and microRNA precursors. A luciferase reporter assay was employed to detect the direct binding of miR-29b to DNMT3A/3B 3′ UTRs. Co-IP was utilized for investigating Id-1 binding activity. Results: miR-29b was negatively correlated with DNMT3A/3B expression at the cellular/histological levels. miR-29b silencing was correlated with increased DNMT3A/3B levels, whereasmiR-29b over-expression caused DNMT3A/3B down-regulation. Luciferase reporter assays confirmed that the miR-29b-mediated downregulation of DNMT3A/3Boccurred through the direct targeting of theirmRNAs'3'-UTRs,whereasBGS assays found that DNMT3A/3B knockdown increased miR-29b expression via CpG island promoter hypomethylation, thus suggesting a crucial crosstalk betweenmiR-29b and DNMT3A/3B via a double-negative feedback loop. Co-IP assay confirmed direct binding between DNMT3A and Id-1. Conclusion: Taken together, our study sheds light on a novel epigenetic circuitry regulating EOC progression and may provide novel options for miR-29b-based epi-therapeutic approaches for future EOC treatment.http://www.karger.com/Article/FullText/447926Micro-RNAsDNA methyltransferase(DNMT)EpigeneticsEpithelial Ovarian Cancer(EOC) |
| spellingShingle | Yue Teng Xiaohang Zuo Meng Hou Yan Zhang Chen Li Wenjuan Luo Xu Li A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression Cellular Physiology and Biochemistry Micro-RNAs DNA methyltransferase(DNMT) Epigenetics Epithelial Ovarian Cancer(EOC) |
| title | A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression |
| title_full | A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression |
| title_fullStr | A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression |
| title_full_unstemmed | A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression |
| title_short | A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression |
| title_sort | double negative feedback interaction between microrna 29b and dnmt3a 3b contributes to ovarian cancer progression |
| topic | Micro-RNAs DNA methyltransferase(DNMT) Epigenetics Epithelial Ovarian Cancer(EOC) |
| url | http://www.karger.com/Article/FullText/447926 |
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