Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation
Increasing evidence highlights the important roles of microRNAs in mediating p53’s tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an...
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| Format: | Article |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/15978 |
| _version_ | 1811200193627947008 |
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| author | Bo Cao Kebing Wang Jun-Ming Liao Xiang Zhou Peng Liao Shelya X Zeng Meifang He Lianzhou Chen Yulong He Wen Li Hua Lu |
| author_facet | Bo Cao Kebing Wang Jun-Ming Liao Xiang Zhou Peng Liao Shelya X Zeng Meifang He Lianzhou Chen Yulong He Wen Li Hua Lu |
| author_sort | Bo Cao |
| collection | DOAJ |
| description | Increasing evidence highlights the important roles of microRNAs in mediating p53’s tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p. |
| first_indexed | 2024-04-12T01:59:35Z |
| format | Article |
| id | doaj.art-bfaecc957e004174850341f777291784 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:59:35Z |
| publishDate | 2016-07-01 |
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| spelling | doaj.art-bfaecc957e004174850341f7772917842022-12-22T03:52:42ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.15978Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activationBo Cao0Kebing Wang1Jun-Ming Liao2Xiang Zhou3Peng Liao4Shelya X Zeng5Meifang He6Lianzhou Chen7Yulong He8Wen Li9Hua Lu10https://orcid.org/0000-0002-9285-7209Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesLaboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesDepartment of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesDepartment of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesDepartment of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesLaboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaLaboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaLaboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United StatesIncreasing evidence highlights the important roles of microRNAs in mediating p53’s tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p.https://elifesciences.org/articles/15978p53miR-139-5pPDE4DBIMapoptosistumor suppression |
| spellingShingle | Bo Cao Kebing Wang Jun-Ming Liao Xiang Zhou Peng Liao Shelya X Zeng Meifang He Lianzhou Chen Yulong He Wen Li Hua Lu Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation eLife p53 miR-139-5p PDE4D BIM apoptosis tumor suppression |
| title | Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation |
| title_full | Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation |
| title_fullStr | Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation |
| title_full_unstemmed | Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation |
| title_short | Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation |
| title_sort | inactivation of oncogenic camp specific phosphodiesterase 4d by mir 139 5p in response to p53 activation |
| topic | p53 miR-139-5p PDE4D BIM apoptosis tumor suppression |
| url | https://elifesciences.org/articles/15978 |
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